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  • 1. Agosta, Lorenzo
    et al.
    Brandt, Erik G.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Lyubartsev, Alexander
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Improved Sampling in Ab Initio Free Energy Calculations of Biomolecules at Solid-Liquid Interfaces: Tight-Binding Assessment of Charged Amino Acids on TiO2 Anatase (101)2020In: Computation, E-ISSN 2079-3197, Vol. 8, no 1, article id 12Article in journal (Refereed)
    Abstract [en]

    Atomistic simulations can complement the scarce experimental data on free energies of molecules at bio-inorganic interfaces. In molecular simulations, adsorption free energy landscapes are efficiently explored with advanced sampling methods, but classical dynamics is unable to capture charge transfer and polarization at the solid-liquid interface. Ab initio simulations do not suffer from this flaw, but only at the expense of an overwhelming computational cost. Here, we introduce a protocol for adsorption free energy calculations that improves sampling on the timescales relevant to ab initio simulations. As a case study, we calculate adsorption free energies of the charged amino acids Lysine and Aspartate on the fully hydrated anatase (101) TiO2 surface using tight-binding forces. We find that the first-principle description of the system significantly contributes to the adsorption free energies, which is overlooked by calculations with previous methods.

  • 2.
    Agosta, Lorenzo
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Brandt, Erik G.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Diffusion and reaction pathways of water near fully hydrated TiO2 surfaces from ab initio molecular dynamics2017In: Journal of Chemical Physics, ISSN 0021-9606, E-ISSN 1089-7690, Vol. 147, no 2, article id 024704Article in journal (Refereed)
    Abstract [en]

    Ab initio molecular dynamics simulations are reported forwater-embedded TiO2 surfaces to determine the diffusive and reactive behavior at full hydration. A three-domain model is developed for six surfaces [rutile (110), (100), and (001), and anatase (101), (100), and (001)] which describes waters as hard (irreversibly bound to the surface), soft (with reduced mobility but orientation freedom near the surface), or bulk. The model explains previous experimental data and provides a detailed picture of water diffusion near TiO2 surfaces. Water reactivity is analyzed with a graph-theoretic approach that reveals a number of reaction pathways on TiO2 which occur at full hydration, in addition to direct water splitting. Hydronium (H3O+) is identified to be a key intermediate state, which facilitates water dissociation by proton hopping between intact and dissociated waters near the surfaces. These discoveries significantly improve the understanding of nanoscale water dynamics and reactivity at TiO2 interfaces under ambient conditions.

  • 3.
    Agosta, Lorenzo
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Brandt, Erik G.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Improved Sampling in Ab Initio-Based Free Energy Calculations of Amino Acids at Solid-Liquid Interfaces: A Tight-Binding Assessment on TiO2 Anatase (101)Manuscript (preprint) (Other academic)
    Abstract [en]

    Atomistic simulations are powerful for probing molecules at bioinorganic interfaces and excellent complements to scarcely available experimental techniques. The free energy controls the adsorption behavior of molecules on nanosurfaces, and is therefore a quantity of particular importance. Advanced sampling techniques can efficiently explore the adsorption free energy landscape, but molecular simulations with classical (Newtownian) dynamics fail to capture charge transfer and polarization at the solid-liquid interface. First principle simulations do not suffer from this limitation but come with a heavy computational load. Here, we introduce an efficient protocol to explore the free energy of adsorption in the ab initio framework. This approach accurately models the complex phenomena at bio-inorganic surfaces on the nanoscale and properly samples the relevant thermodynamic properties. We present a case study of adsorption of the Lysine and Aspartate amino acids on the anatase (101) TiO2 surface with the tight binding method. The high values of the calculated adsorption free energies highlight the importance of a proper description of the electronic state for surface binding processes.

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  • 4. Atzori, Alessio
    et al.
    Liggi, Sonia
    Laaksonen, Aatto
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK). Stockholm University, Science for Life Laboratory (SciLifeLab). University of Cagliari, Italy.
    Porcu, Massimiliano
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK). Università di Cagliari, Italy.
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Saba, Giuseppe
    Mocci, Francesca
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK). Stockholm University, Science for Life Laboratory (SciLifeLab). Università di Cagliari, Italy.
    Base sequence specificity of counterion binding to DNA: what can MD simulations tell us?2016In: Canadian journal of chemistry (Print), ISSN 0008-4042, E-ISSN 1480-3291, Vol. 94, no 12, p. 1181-1188Article in journal (Refereed)
    Abstract [en]

    Nucleic acids are highly charged biopolymers whose secondary structure is strongly dependent on electrostatic interactions. Solvent molecules and ions are also believed to play an important role in mediating and directing both sequence recognition and interactions with other molecules, such as proteins and a variety of ligands. Therefore, to fully understand the biological functions of DNA, it is necessary to understand the interactions with the surrounding counterions. It is well known that monovalent counterions can bind to the minor groove of DNA with consecutive sequences of four, or more, adenine and thymine (A-tracts) with relatively long residence times. However, much less is known about their binding to the backbone and to the major groove. In this work, we used molecular dynamics simulations to both investigate the interactions between the backbone and major groove of DNA and one of its physiological counterions (Na+) and evaluate the relationship between these interactions and the nucleotide sequence. Three dodecamers, namely CGAAAATTTTCG, CGCTCTAGAGCG, and CGCGAATTCGCG, were simulated using the Toukan-Rahman flexible SPC water model and Smith and Dang parameters for Na+, revealing a significant sequence dependence on the ion binding to both backbone and major groove. In the absence of experimental data on the atomistic details of the studied interactions, the reliability of the results was evaluated performing the simulations with additional sets of potential parameters for ions and solvent, namely the A. qvist or the Joung and Cheatham ion parameters and the TIP3P water model. This allowed us to evaluate the results by verifying which features are preserved independently from the parameters adopted.

  • 5.
    B. Brant Carvalho, Paulo H.
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Ivanov, Mikhail
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Andersson, Ove
    Loerting, Thomas
    Bauer, Marion
    Tulk, Chris A.
    Haberl, Bianca
    Daemen, Luke L.
    Molaison, Jamie J.
    Amann-Winkel, Katrin
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Bull, Craig L.
    Funnell, Nicholas P.
    Häussermann, Ulrich
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Neutron scattering study of polyamorphic THF·17(H2O) – toward a generalized picture of amorphous states and structures derived from clathrate hydrates2023In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, no 21Article in journal (Refereed)
    Abstract [en]

    From crystalline tetrahydrofuran clathrate hydrate, THF–CH (THF·17H2O, cubic structure II), three distinct polyamorphs can be derived. First, THF–CH undergoes pressure-induced amorphization when pressurized to 1.3 GPa in the temperature range 77–140 K to a form which, in analogy to pure ice, may be called high-density amorphous (HDA). Second, HDA can be converted to a densified form, VHDA, upon heat-cycling at 1.8 GPa to 180 K. Decompression of VHDA to atmospheric pressure below 130 K produces the third form, recovered amorphous (RA). Results from neutron scattering experiments and molecular dynamics simulations provide a generalized picture of the structure of amorphous THF hydrates with respect to crystalline THF–CH and liquid THF·17H2O solution (∼2.5 M). Although fully amorphous, HDA is heterogeneous with two length scales for water–water correlations (less dense local water structure) and guest–water correlations (denser THF hydration structure). The hydration structure of THF is influenced by guest–host hydrogen bonding. THF molecules maintain a quasiregular array, reminiscent of the crystalline state, and their hydration structure (out to 5 Å) constitutes ∼23H2O. The local water structure in HDA is reminiscent of pure HDA-ice featuring 5-coordinated H2O. In VHDA, the hydration structure of HDA is maintained but the local water structure is densified and resembles pure VHDA-ice with 6-coordinated H2O. The hydration structure of THF in RA constitutes ∼18 H2O molecules and the water structure corresponds to a strictly 4-coordinated network, as in the liquid. Both VHDA and RA can be considered as homogeneous.

  • 6.
    B. Brant Carvalho, Paulo H.
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Mace, Amber
    Andersson, Ove
    Tulk, Chris A.
    Molaison, Jamie
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Nangoi, Inna M.
    Leitão, Alexandre A.
    Häussermann, Ulrich
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Pressure-induced amorphization of noble gas clathrate hydrates2021In: Physical Review B, ISSN 2469-9950, E-ISSN 2469-9969, Vol. 103, no 6, article id 064205Article in journal (Refereed)
    Abstract [en]

    The high-pressure structural behavior of the noble gas (Ng) clathrate hydrates Ar center dot 6.5 H2O and Xe center dot 7.2 H2O featuring cubic structures II and I, respectively, was investigated by neutron powder diffraction (using the deuterated analogues) at 95 K. Both hydrates undergo pressure-induced amorphization (PIA), indicated by the disappearance of Bragg diffraction peaks, but at rather different pressures, at 1.4 and above 4.0 GPa, respectively. Amorphous Ar hydrate can be recovered to ambient pressure when annealed at >1.5 GPa and 170 K and is thermally stable up to 120 K. In contrast, it was impossible to retain amorphous Xe hydrate at pressures below 3 GPa. Molecular dynamics (MD) simulations were used to obtain general insight into PIA of Ng hydrates, from Ne to Xe. Without a guest species, both cubic clathrate structures amorphize at 1.2 GPa, which is very similar to hexagonal ice. Filling of large-sized H cages does not provide stability toward amorphization for structure II, whereas filled small-sized dodecahedral D cages shift PIA successively to higher pressures with increasing size of the Ng guest. For structure I, filling of both kinds of cages, large-sized T and small-sized D, acts to stabilize in a cooperative fashion. Xe hydrate represents a special case. In MD, disordering of the guest hydration structure is already seen at around 2.5 GPa. However, the different coordination numbers of the two types of guests in the crystalline cage structure are preserved, and the state is shown to produce a Bragg diffraction pattern. The experimentally observed diffraction up to 4 GPa is attributed to this semicrystalline state.

  • 7.
    B. Brant Carvalho, Paulo H.
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Mace, Amber
    Nangoi, Inna Martha
    Leitão, Alexandre A.
    Tulk, Chris A.
    Molaison, Jamie J.
    Andersson, Ove
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Häussermann, Ulrich
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Exploring High-Pressure Transformations in Low-Z (H2, Ne) Hydrates at Low Temperatures2022In: Crystals, ISSN 2073-4352, Vol. 12, no 1, article id 9Article in journal (Refereed)
    Abstract [en]

    The high pressure structural behavior of H2 and Ne clathrate hydrates with approximate composition H2/Ne·~4H2O and featuring cubic structure II (CS-II) was investigated by neutron powder diffraction using the deuterated analogues at ~95 K. CS-II hydrogen hydrate transforms gradually to isocompositional C1 phase (filled ice II) at around 1.1 GPa but may be metastably retained up to 2.2 GPa. Above 3 GPa a gradual decomposition into C2 phase (H2·H2O, filled ice Ic) and ice VIII’ takes place. Upon heating to 200 K the CS-II to C1 transition completes instantly whereas C1 decomposition appears sluggish also at 200 K. C1 was observed metastably up to 8 GPa. At 95 K C1 and C2 hydrogen hydrate can be retained below 1 GPa and yield ice II and ice Ic, respectively, upon complete release of pressure. In contrast, CS-II neon hydrate undergoes pressure-induced amorphization at 1.9 GPa, thus following the general trend for noble gas clathrate hydrates. Upon heating to 200 K amorphous Ne hydrate crystallizes as a mixture of previously unreported C2 hydrate and ice VIII’.

  • 8.
    B. Brant Carvalho, Paulo H.
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK). Stockholm Univ, Dept Mat & Environm Chem, SE-10691 Stockholm, Sweden.
    Moraes, Pedro Ivo R.
    Leitão, Alexandre A.
    Andersson, Ove
    Tulk, Chris A.
    Molaison, Jamie
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Häussermann, Ulrich
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Structural investigation of three distinct amorphous forms of Ar hydrate2021In: RSC Advances, E-ISSN 2046-2069, Vol. 11, no 49, p. 30744-30754Article in journal (Refereed)
    Abstract [en]

    Three amorphous forms of Ar hydrate were produced using the crystalline clathrate hydrate Ar·6.5H2O (structure II, Fdm, a ≈ 17.1 Å) as a precursor and structurally characterized by a combination of isotope substitution (36Ar) neutron diffraction and molecular dynamics (MD) simulations. The first form followed from the pressure-induced amorphization of the precursor at 1.5 GPa at 95 K and the second from isobaric annealing at 2 GPa and subsequent cooling back to 95 K. In analogy to amorphous ice, these amorphs are termed high-density amorphous (HDA) and very-high-density amorphous (VHDA), respectively. The third amorph (recovered amorphous, RA) was obtained when recovering VHDA to ambient pressure (at 95 K). The three amorphs have distinctly different structures. In HDA the distinction of the original two crystallographically different Ar guests is maintained as differently dense Ar–water hydration structures, which expresses itself in a split first diffraction peak in the neutron structure factor function. Relaxation of the local water structure during annealing produces a homogeneous hydration environment around Ar, which is accompanied with a densification by about 3%. Upon pressure release the homogeneous amorphous structure undergoes expansion by about 21%. Both VHDA and RA can be considered frozen solutions of immiscible Ar and water in which in average 15 and 11 water molecules, respectively, coordinate Ar out to 4 Å. The local water structures of HDA and VHDA Ar hydrates show some analogy to those of the corresponding amorphous ices, featuring H2O molecules in 5- and 6-fold coordination with neighboring molecules. However, they are considerably less dense. Most similarity is seen between RA and low density amorphous ice (LDA), which both feature strictly 4-coordinated H2O networks. It is inferred that, depending on the kind of clathrate structure and occupancy of cages, amorphous states produced from clathrate hydrates display variable local water structures.

  • 9.
    Barros Brant Carvalho, Paulo Henrique
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Ivanov, Mikhail
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Andersson, Ove
    Department of Physics, Umeå University.
    Loerting, Thomas
    Institute of Physical Chemistry, University of Innsbruck.
    Bauer, Marion
    Institute of Physical Chemistry, University of Innsbruck.
    Tulk, Chris A.
    Neutron Scattering Division, Oak Ridge National Laboratory.
    Haberl, Bianca
    Neutron Scattering Division, Oak Ridge National Laboratory.
    Daemen, Luke L.
    Neutron Scattering Division, Oak Ridge National Laboratory.
    Molaison, Jamie J.
    Neutron Scattering Division, Oak Ridge National Laboratory.
    Amann-Winkel, Katrin
    Stockholm University, Faculty of Science, Department of Physics.
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry. Stockholm University, Faculty of Science, Department of Physics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Bull, Craig L.
    ISIS Neutron and Muon Source, Rutherford Appleton Laboratory.
    Funnell, Nicholas P.
    ISIS Neutron and Muon Source, Rutherford Appleton Laboratory.
    Häussermann, Ulrich
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Inorganic and Structural Chemistry.
    Neutron scattering study of polyamorphic THF ∙ (H2O)17 – toward a generalized picture of amorphous states and structures derived from clathrate hydratesManuscript (preprint) (Other academic)
    Abstract [en]

    From crystalline tetrahydrofuran clathrate hydrate, THF-CH (THF ∙ 17H2O, cubic structure II), three distinct polyamorphs can be derived. First, THF-CH undergoes pressure-induced amorphization when pressurized to 1.3 GPa in the temperature range 77–140 K to a form which, in analogy to pure ice, may be called high-density amorphous (HDA). Second, HDA can be converted to a densified form, very-HDA (VHDA), upon heat-cycling at 1.8 GPa to 180 K. Decompression of VHDA to atmospheric pressure below 130 K produces the third, recovered amorphous (RA) form. Results from a compilation of neutron scattering experiments and molecular dynamics simulations provide a generalized picture of the structure of amorphous THF hydrates with respect to crystalline THF-CH and liquid THF ∙ 17H2O solution (~2.5 M). The calculated density of (only in situ observable) HDA and VHDA at 2 GPa and 130 K is 1.287 and 1.328 g/cm3, respectively, whereas that of RA (at 1 atm) is 1.081 g/cm3. Although fully amorphous, HDA is heterogeneous with two length scales for water-water correlations (less dense local water structure) and guest-water correlations (denser THF hydration structure). The hydration structure of THF is influenced by guest-host hydrogen bonding. THF molecules maintain a quasiregular array, reminiscent of the crystalline state, and their hydration structure (out to 5 Å) constitutes ~23 H2O. The local water structure in HDA is reminiscent of pure HDA-ice, featuring 5-coordinated H2O. In VHDA, this structure is maintained but the local water structure is densified to resemble pure VHDA-ice with 6-coordinated H2O. The hydration structure of THF in RA constitutes ~18 H2O and the water structure corresponds to a strictly 4-coordinated network, as in the liquid. Both VHDA and RA can be considered as homogeneous, solid solutions of THF and water. The local water structure of water-rich (1:17) amorphous CHs resembles most that of the corresponding amorphous water ices when compared to guest-rich CHs, e.g., Ar ∙ ~6H2O. The proposed significance of different contributions of water local environments presents a simple view to justify neutron structure factor features.

  • 10.
    Brandt, Erik G.
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Agosta, Lorenzo
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Reactive wetting properties of TiO2 nanoparticles predicted by ab initio molecular dynamics simulations2016In: Nanoscale, ISSN 2040-3364, E-ISSN 2040-3372, Vol. 8, no 27, p. 13385-13398Article in journal (Refereed)
    Abstract [en]

    Small-sized wet TiO2 nanoparticles have been investigated by ab initio molecular dynamics simulations. Chemical and physical adsorption of water on the TiO2-water interface was studied as a function of water content, ranging from dry nanoparticles to wet nanoparticles with monolayer coverage of water. The surface reactivity was shown to be a concave function of water content and driven by surface defects. The local coordination number at the defect was identified as the key factor to decide whether water adsorption proceeds through dissociation or physisorption on the surface. A consistent picture of TiO2 nanoparticle wetting at the microscopic level emerges, which corroborates existing experimental data and gives further insight into the molecular mechanisms behind nanoparticle wetting. These calculations will facilitate the engineering of metal oxide nanoparticles with a controlled catalytic water activity.

  • 11.
    Brandt, Erik G.
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Molecular Dynamics Simulations of Adsorption of Amino Acid Side Chain Analogues and a Titanium Binding Peptide on the TiO2 (100) Surface2015In: The Journal of Physical Chemistry C, ISSN 1932-7447, E-ISSN 1932-7455, Vol. 119, no 32, p. 18126-18139Article in journal (Refereed)
    Abstract [en]

    Adsorption profiles and adsorption free energies were determined for the side chain analogues of the 20 naturally occurring amino acids and a titanium binding peptide on the TiO2 (100) surface. Microsecond simulations with umbrella sampling and metadynamics were used to sample the free energy barriers associated with desolvation of strongly bound water molecules at the TiO2 surface. Polar and aromatic side chain analogues that hydrogen bond either to surface waters or directly to the metal oxide surface were found to be the strongest binders. Further, adsorption simulations of a 6 residue titanium binding peptide identified two binding modes on TiO2 (100). The peptide structure with lowest free energy was shown to be stabilized by a salt bridge between the end termini. A comparison between the free energies of the side chain analogues of the peptide sequence and the peptide itself shows that the free energy contributions are not additive. The simulations emphasize that tightly bound surface waters play a key role for peptide and protein structures when bound to inorganic surfaces in biological environments.

  • 12.
    Brandt, Erik G.
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Systematic Optimization of a Force Field for Classical Simulations of TiO2-Water Interfaces2015In: The Journal of Physical Chemistry C, ISSN 1932-7447, E-ISSN 1932-7455, Vol. 119, no 32, p. 18110-18125Article in journal (Refereed)
    Abstract [en]

    Atomistic force field parameters were developed for the TiO2-water interface by systematic optimization with respect to experimentally determined crystal structures (lattice parameters) and surface thermodynamics (water adsorption enthalpy). Optimized force field parameters were determined for the two cases where TiO2 was modeled with or without covalent bonding. The nonbonded TiO2 model can be used to simulate different TiO2 phases, while the bonded TiO2 model is particularly useful for simulations of nanosized TiO2 and biomatter, including protein-surface and nanoparticle-biomembrane simulations. The procedure is easily generalized to parametrize interactions between other inorganic surfaces and biomolecules.

  • 13.
    Dong, Kun
    et al.
    Institute of Process Engineering, Chinese Academy of Sciences, 100190 Beijing, China.
    Zhou, Guohui
    Institute of Process Engineering, Chinese Academy of Sciences, 100190 Beijing, China.
    Liu, Xiaomin
    Institute of Process Engineering, Chinese Academy of Sciences, 100190 Beijing, China.
    Yao, Xiaoguian
    Institute of Process Engineering, Chinese Academy of Sciences, 100190 Beijing, China.
    Zhang, Suojiang
    Institute of Process Engineering, Chinese Academy of Sciences, 100190 Beijing, China.
    Lyubartsev, Alexander
    Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry.
    Structural Evidence for the Ordered Crystallites of Ionic Liquid in Confined Carbon Nanotubes2009In: The Journal of Physical Chemistry C, ISSN 1932-7447, E-ISSN 1932-7455, Vol. 113, no 23, p. 10013-10020Article in journal (Refereed)
    Abstract [en]

    Ionic liquids (ILs) are a class of new green materials that have attracted extensive attention in recent decades. Many novel properties not evident under normal conditions may appear when ionic liquids are confined to a nanometer scale. As was observed in the experiment, an anomalous phase behavior from liquid to high melting point perfect crystal occurred when 1-n-butyl-3-methylimidazolium hexafluorophosphate ([bmim][PF6]) ionic liquid was confined in a carbon nanotube. In this work, we performed molecular dynamics (MD) simulations for [bmim][PF6] ionic liquid and provided direct structural evidence that the ionic crystallizes in a carbon nanotube. The ordered ionic arrangement in both the radial and the axial directions can be observed inside the channels of the CNTs to induce the form of crystallites. The ionic stacking and distributing can be determined by the sizes of the CNTs. Hydrogen bonds remain the dominant interactions between cations and anions when the ionic liquid enters into the CNT from the bulk phase. The free energies as the thermal driven forces were calculated, and it is found that it is very difficult for a single anion to enter into the channel of the CNT spontaneously. A more favorable way is through an ion-pair in which a cation “pulls” an anion to enter into the channel of the CNT together. It is predicted that other ionic liquids that possess similar structures, even including the pyridinium-based ionic liquids, can show higher melting points when confined in CNTs.

  • 14. Egorov, Andrei V.
    et al.
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Laaksonen, Aatto
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Molecular Dynamics Simulation Study of Glycerol-Water Liquid Mixtures2011In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 115, no 49, p. 14572-14581Article in journal (Refereed)
    Abstract [en]

    To study the effects of water on conformational dynamics of polyalcohols, Molecular Dynamics simulations of glycerol water liquid mixtures have been carried out at different concentrations: 42.9 and 60.0 wt 96 of glycerol, respectively. On the basis of the analysis of backbone conformer distributions, it is found that the surrounding water molecules have a large impact on the populations of the glycerol conformers. While the local structure of water in the liquid mixture is surprisingly close to that in pure liquid water, the behavior of glycerols can be divided into three different categories where roughly 25% of them occur in a structure similar to that in pure liquid of glycerol, ca. 25% of them exist as monomers, solvated by water, and the remaining 50% of glycerols in the mixture form H-bonded strings as. remains of the glycerol H-bond network. The typical glycerol H-bond network still exists even at the lower concentration of 40 wt % of glycerol. The microheterogeneity of water glycerol mixtures is analyzed using time-averaged distributions of the sizes of the water aggregates. At 40 wt % of glycerol, the cluster sizes from 3 to 10 water molecules are observed. The increase of glycerol content causes a depletion of clusters leading to smaller 3-5 molecule clusters domination. Translational diffusion coefficients have been calculated to study the dynamical behavior of both glycerol and water molecules. Rotational-reorientational motion is studied both in overall and in selected substructures on the basis of time correlation functions. Characteristic time scales for different motional modes are deduced on the basis of the calculated correlation times. The general conclusion is that the presence of water increases the overall mobility of glycerol, while glycerol slows the mobility of water.

  • 15.
    Elias-Wolff, Federico
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Lindén, Martin
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Brandt, Erik G.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Curvature sensing by cardiolipin in simulated buckled membranes2019In: Soft Matter, ISSN 1744-683X, E-ISSN 1744-6848, Vol. 15, no 4, p. 792-802Article in journal (Refereed)
    Abstract [en]

    Cardiolipin is a non-bilayer phospholipid with a unique dimeric structure. It localizes to negative curvature regions in bacteria and is believed to stabilize respiratory chain complexes in the highly curved mitochondrial membrane. Cardiolipin's localization mechanism remains unresolved, because important aspects such as the structural basis and strength for lipid curvature preferences are difficult to determine, partly due to the lack of efficient simulation methods. Here, we report a computational approach to study curvature preferences of cardiolipin by simulated membrane buckling and quantitative modeling. We combine coarse-grained molecular dynamics with simulated buckling to determine the curvature preferences in three-component bilayer membranes with varying concentrations of cardiolipin, and extract curvature-dependent concentrations and lipid acyl chain order parameter profiles. Cardiolipin shows a strong preference for negative curvatures, with a highly asymmetric chain order parameter profile. The concentration profiles are consistent with an elastic model for lipid curvature sensing that relates lipid segregation to local curvature via the material constants of the bilayers. These computations constitute new steps to unravel the molecular mechanism by which cardiolipin senses curvature in lipid membranes, and the method can be generalized to other lipids and membrane components as well.

  • 16.
    Elías-Wolff, Federico
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Lindén, Martin
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Brandt, Erik G.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Computing Curvature Sensitivity of Biomolecules in Membranes by Simulated Buckling2018In: Journal of Chemical Theory and Computation, ISSN 1549-9618, E-ISSN 1549-9626, Vol. 14, no 3, p. 1643-1655Article in journal (Refereed)
    Abstract [en]

    Membrane curvature sensing, where the binding free energies of membrane-associated molecules depend on the local membrane curvature, is a key factor to modulate and maintain the shape and organization of cell membranes. However, the microscopic mechanisms are not well understood, partly due to absence of efficient simulation methods. Here, we describe a method to compute the curvature dependence of the binding free energy of a membrane associated probe molecule that interacts with a buckled membrane, which has been created by lateral compression of a flat bilayer patch. This buckling approach samples a wide range of curvatures in a single simulation, and anisotropic effects can be extracted from the orientation statistics. We develop an efficient and robust algorithm to extract the motion of the probe along the buckled membrane surface, and evaluate its numerical properties by extensive sampling of three coarse-grained model systems: local lipid density in a curved environment for single-component bilayers, curvature preferences of individual lipids in two-component membranes, and curvature sensing by a homotrimeric transmembrane protein. The method can be used to complement experimental data from curvature partition assays and provides additional insight into mesoscopic theories and molecular mechanisms for curvature sensing.

  • 17.
    Elías-Wolff, Federico
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Lindén, Martin
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Brandt, Erik G.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Curvature sensing by cardiolipin in simulated buckled membranesIn: Article in journal (Refereed)
  • 18.
    Ermilova, Inna
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Lyubartsev, Alexander
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Modelling of interactions between Aβ(25-35) peptide and phospholipid bilayers: effects of cholesterol and lipid saturation2020In: RSC Advances, E-ISSN 2046-2069, Vol. 10, no 7, p. 3902-3915Article in journal (Refereed)
    Abstract [en]

    Aggregation of amyloid beta (Aβ) peptides in neuronal membranes is a known promoter of Alzheimer’s disease. To gain insight into the molecular details of Aβ peptide aggregation and its effect on model neuronal membranes, we carried out molecular dynamics simulations of the Aβ(25–35) fragment of the amyloid precursor protein in phospholipid bilayers composed of either fully saturated or highly unsaturated lipids, in the presence or absence of cholesterol. It was found that the peptide does not penetrate through any of the considered membranes, but can reside in the headgroup region and upper part of the lipid tails showing a clear preference to a polyunsaturated cholesterol-free membrane. Due to the ordering and condensing effect upon addition of cholesterol, membranes become more rigid facilitating peptide aggregation on the surface. Except for the case of the cholesterol-free saturated lipid bilayer, the peptides have a small effect on the membrane structure and ordering. It was also found that the most “active” amino-acid for peptide–lipid and peptide–cholesterol interaction is methionine-35, followed by asparagine-27 and serine-26, which form hydrogen bonds between peptides and polar atoms of lipid headgroups. These amino acids are also primarily responsible for peptide aggregation. This work will be relevant for designing strategies to develop drugs to combat Alzheimer’s disease.

  • 19.
    Ermilova, Inna
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Cholesterol in phospholipid bilayers: positions and orientations inside membranes with different unsaturation degrees2019In: Soft Matter, ISSN 1744-683X, E-ISSN 1744-6848, Vol. 15, no 1, p. 78-93Article in journal (Refereed)
    Abstract [en]

    Cholesterol is an essential component of all animal cell membranes and plays an important role in maintaining the membrane structure and physical–chemical properties necessary for correct cell functioning. The presence of cholesterol is believed to be responsible for domain formation (lipid rafts) due to different interactions of cholesterol with saturated and unsaturated lipids. In order to get detailed atomistic insight into the behaviour of cholesterol in bilayers composed of lipids with varying degrees of unsaturation, we have carried out a series of molecular dynamics simulations of saturated and polyunsaturated lipid bilayers with different contents of cholesterol, as well as well-tempered metadynamics simulations with a single cholesterol molecule in these bilayers. From these simulations we have determined distributions of cholesterol across the bilayer, its orientational properties, free energy profiles, and specific interactions of molecular groups able to form hydrogen bonds. Both molecular dynamics and metadynamics simulations showed that the most unsaturated bilayer with 22:6 fatty acid chains shows behaviour which is most different from other lipids. In this bilayer, cholesterol is relatively often found in a “flipped” configuration with the hydroxyl group oriented towards the membrane middle plane. This bilayer has also the highest (least negative) binding free energy among liquid phase bilayers, and the lowest reorientation barrier. Furthermore, cholesterol molecules in this bilayer are often found to form head-to-tail contacts which may lead to specific clustering behaviour. Overall, our simulations support ideas that there can be a subtle interconnection between the contents of highly unsaturated fatty acids and cholesterol, deficiency or excess of each of them is related to many human afflictions and diseases.

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  • 20.
    Ermilova, Inna
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Extension of the Slipids Force Field to Polyunsaturated Lipids2016In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 120, no 50, p. 12826-12842Article in journal (Refereed)
    Abstract [en]

    The all-atomic force field Slipids (Stockholm Lipids) for lipid bilayers simulations has been extended to polyunsaturated lipids. Following the strategy adopted in the development of previous versions of the Slipids force field, the parametrization was essentially based on high-level ab initio calculations. Atomic charges and torsion angles related to polyunsaturated lipid tails were parametrized using structures of dienes molecules. The new parameters of the force field were validated in simulations of bilayers composed of seven polyunsaturated lipids. An overall good agreement was found with available experimental data on the areas per lipids, volumetric properties of bilayers, deuterium order parameters, and scattering form factors. Furthermore, simulations of bilayers consisting of highly polyunsaturated lipids and cholesterol molecules have been carried out. The majority of cholesterol molecules were found in a position parallel to bilayer normal with the hydroxyl group directed to the membrane surface, while a small fraction of cholesterol was found in the bilayer center parallel to the membrane plane. Furthermore, a tendency of cholesterol molecules to form chain-like clusters in polyunsaturated bilayers was qualitatively observed.

  • 21.
    Ermilova, Inna
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Stenberg, Samuel
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Quantum chemical and molecular dynamics modelling of hydroxylated polybrominated diphenyl ethers2017In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 19, no 41, p. 28263-28274Article in journal (Refereed)
    Abstract [en]

    A series of 19 hydroxylated polybrominated diphenyl ethers (OH-PBDEs) have been studied using density functional theory (DFT) and molecular dynamics simulations with the purpose of investigating eventual correlations between their physicochemical properties and toxic action. Dissociation constants (pK(a)), solvation free energies and octanol-water partition coefficients (logP) have been computed. Additionally, metadynamics simulations of OH-PBDEs passing through a lipid bilayer have been carried out for four OH-PBDE species. No correlations between computed pKa values and toxicity data have been found. Medium correlations were found between partition coefficients and the ability of OH-PBDEs to alter membrane potential in cell cultures, which is attributed to higher uptake of molecules with larger log P parameters. It was also demonstrated that in lipid bilayers, OH-PBDE molecules differ in their orientational distributions and can adopt different conformations which can affect the uptake of these molecules and influence the pathways of their toxic action.

  • 22. Fan, Yanping
    et al.
    Korolev, Nikolay
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Nordenskiöld, Lars
    An Advanced Coarse-Grained Nucleosome Core Particle Model for Computer Simulations of Nucleosome-Nucleosome Interactions under Varying Ionic Conditions2013In: PLOS ONE, E-ISSN 1932-6203, Vol. 8, no 2, article id e54228Article in journal (Refereed)
    Abstract [en]

    In the eukaryotic cell nucleus, DNA exists as chromatin, a compact but dynamic complex with histone proteins. The first level of DNA organization is the linear array of nucleosome core particles (NCPs). The NCP is a well-defined complex of 147 bp DNA with an octamer of histones. Interactions between NCPs are of paramount importance for higher levels of chromatin compaction. The polyelectrolyte nature of the NCP implies that nucleosome-nucleosome interactions must exhibit a great influence from both the ionic environment as well as the positively charged and highly flexible N-terminal histone tails, protruding out from the NCP. The large size of the system precludes a modelling analysis of chromatin at an all-atom level and calls for coarse-grained approximations. Here, a model of the NCP that include the globular histone core and the flexible histone tails described by one particle per each amino acid and taking into account their net charge is proposed. DNA wrapped around the histone core was approximated at the level of two base pairs represented by one bead (bases and sugar) plus four beads of charged phosphate groups. Computer simulations, using a Langevin thermostat, in a dielectric continuum with explicit monovalent (K+), divalent (Mg2+) or trivalent (Co(NH3)(6)(3+)) cations were performed for systems with one or ten NCPs. Increase of the counterion charge results in a switch from repulsive NCP-NCP interaction in the presence of K+, to partial aggregation with Mg2+ and to strong mutual attraction of all 10 NCPs in the presence of CoHex(3+). The new model reproduced experimental results and the structure of the NCP-NCP contacts is in agreement with available data. Cation screening, ion-ion correlations and tail bridging contribute to the NCP-NCP attraction and the new NCP model accounts for these interactions.

  • 23.
    Faure, Bertrand
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Wetterskog, Erik
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Gunnarsson, Klas
    Josten, Elisabeth
    Hermann, Raphael P.
    Brueckel, Thomas
    Andreasen, Jens Wenzel
    Meneau, Florian
    Meyer, Mathias
    Lyubartsev, Alexander
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Bergström, Lennart
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Salazar-Alvarez, German
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Svedlindh, Peter
    2D to 3D crossover of the magnetic properties in ordered arrays of iron oxide nanocrystals2013In: Nanoscale, ISSN 2040-3364, E-ISSN 2040-3372, Vol. 5, no 3, p. 953-960Article in journal (Refereed)
    Abstract [en]

    The magnetic 2D to 3D crossover behavior of well-ordered arrays of monodomain gamma-Fe2O3 spherical nanoparticles with different thicknesses has been investigated by magnetometry and Monte Carlo (MC) simulations. Using the structural information of the arrays obtained from grazing incidence small-angle X-ray scattering and scanning electron microscopy together with the experimentally determined values for the saturation magnetization and magnetic anisotropy of the nanoparticles, we show that MC simulations can reproduce the thickness-dependent magnetic behavior. The magnetic dipolar particle interactions induce a ferromagnetic coupling that increases in strength with decreasing thickness of the array. The 2D to 3D transition in the magnetic properties is mainly driven by a change in the orientation of the magnetic vortex states with increasing thickness, becoming more isotropic as the thickness of the array increases. Magnetic anisotropy prevents long-range ferromagnetic order from being established at low temperature and the nanoparticle magnetic moments instead freeze along directions defined by the distribution of easy magnetization directions.

  • 24.
    Grote, Fredrik
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Ermilova, Inna
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Molecular Dynamics Simulations of Furfural and 5-Hydroxymethylfurfural at Ambient and Hydrothermal Conditions2018In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 122, no 35, p. 8416-8428Article in journal (Refereed)
    Abstract [en]

    In this work, we present results from molecular dynamics simulations of aqueous solutions of furfural and 5-hydroxymethylfurfural, which are important intermediates in the hydrothermal carbonization processes of biomass conversion. The computations were performed both at ambient and hydrothermal conditions using a two-level factorial design varying concentration, temperature, and pressure. A number of equilibrium and dynamic properties have been computed including enthalpies and free energies of vaporization, free energies of solvation, diffusion coefficients, and rotational/reorientational correlation times. Structural properties of solutions were analyzed using radial and spatial distribution functions. It was shown that the formation of hydrogen bonds among 5-hydroxymethylfurfural molecules is preferred compared to hydrogen bonding between 5-hydroxymethylfurfural and water. In addition, our results suggest that the oxygen atoms in the furan rings of furfural and 5-hydroxymethylfurfural do not participate in hydrogen bonding to the same extent as the oxygen atoms in the hydroxyl and carbonyl groups. It is also observed that furfural molecules aggregate under certain conditions, and we show how this is affected by changes in temperature, pressure, and concentration in agreement with experimental solubility data. The analysis of the computational results provides useful insight into the structure and dynamics of the considered molecules at conditions of hydrothermal carbonization, as well as at ambient conditions.

  • 25.
    Grote, Fredrik
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Optimization of Slipids Force Field Parameters Describing Headgroups of Phospholipids2020In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 124, no 40, p. 8784-8793Article in journal (Refereed)
    Abstract [en]

    The molecular mechanics force field Slipids developed in a series of works by Jambeck and Lyubartsev (J. Phys. Chem. B 2012, 116, 3164-3179; J. Chem. Theory Comput. 2012, 8, 2938-2948) generally provides a good description of various lipid bilayer systems. However, it was also found that order parameters of C-H bonds in the glycerol moiety of the phosphatidylcholine headgroup deviate significantly from NMR results. In this work, the dihedral force field parameters have been reparameterized in order to improve the agreement with experiment. For this purpose, we have computed energies for a large amount of lipid headgroup conformations using density functional theory on the B3P86/cc-pvqz level and optimized dihedral angle parameters simultaneously to provide the best fit to the quantum chemical energies. The new parameter set was validated for three lipid bilayer systems against a number of experimental properties including order parameters, area per lipid, scattering form factors, bilayer thickness, area compressibility and lateral diffusion coefficients. In addition, the order parameter dependence on cholesterol content in the POPC bilayer was investigated. It is shown that the new force field significantly improves agreement with the experimental order parameters for the lipid headgroup while keeping good agreement with other experimentally measured properties.

  • 26.
    Grote, Fredrik
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Dvinskikh, Sergey V.
    Rinwa, Vibhu
    Holmbäck, Jan
    Phase equilibrium, dynamics and rheology of phospholipid–ethanol mixtures: a combined molecular dynamics, NMR and viscometry study2023In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 25, no 23, p. 15905-15915Article in journal (Refereed)
    Abstract [en]

    Binary mixtures of ethanol and phospholipids DOPC and DOPE have been investigated in a composition range relevant for topical drug delivery applications. This was done using a combined computer simulation and experimental approach where molecular dynamics simulations of ethanol–lipid mixtures with different compositions were performed. Several key properties including diffusion coefficients, longitudinal relaxation times, and shear viscosity were computed. In addition, diffusion coefficients, viscosities and NMR longitudinal relaxation times were measured experimentally for comparison and in order to validate the results from simulation. Diffusion coefficients and relaxation times obtained from simulations are in good agreement with results from NMR and computed viscosities are in reasonable agreement with viscometry experiments indicating that the simulations provide a realistic description of the ethanol–phospholipid mixtures. Structural changes in the simulated systems were investigated using an analysis based on radial distribution functions. This showed that the structure of ethanol–DOPC mixtures remains essentially unchanged in the investigated concentration range while ethanol–DOPE mixtures undergo structural rearrangements with the tendency for forming small aggregates on the 100 ns time scale consisting of less than 10 lipids. Although our simulations and experiments indicate that no larger aggregates form, they also show that DOPE has stronger aggregation tendency than DOPC. This highlights the importance of the character of the lipid headgroup for lipid aggregation in ethanol and gives new insights into phase equilibrium, dynamics and rheology that could be valuable for the development of advanced topical drug delivery formulations.

  • 27. Huang, Congcong
    et al.
    Wikfeldt, K. Thor
    Stockholm University, Faculty of Science, Department of Physics.
    Tokushima, Takashi
    Nordlund, Dennis
    Harada, Yoshi
    Bergmann, Uwe
    Niebuhr, Marc
    Weiss, T. M.
    Horikawa, Yoshi
    Leetmaa, Mikael
    Stockholm University, Faculty of Science, Department of Physics.
    Ljungberg, Mathias P.
    Stockholm University, Faculty of Science, Department of Physics.
    Takahashi, Osamu
    Lenz, Annika
    Ojamäe, Lars
    Lyubartsev, Alexander
    Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry, Physical Chemistry.
    Shin, Shik
    Pettersson, Lars G. M.
    Stockholm University, Faculty of Science, Department of Physics.
    Nilsson, Anders
    Stockholm University, Faculty of Science, Department of Physics.
    The Inhomogeneous Structure of Water at Ambient Conditions2009In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 106, p. 15214-15218Article in journal (Refereed)
    Abstract [en]

    Small-angle X-ray scattering (SAXS) is used to demonstrate the presence of density fluctuations in ambient water on a physical length-scale of ≈1 nm; this is retained with decreasing temperature while the magnitude is enhanced. In contrast, the magnitude of fluctuations in a normal liquid, such as CCl4, exhibits no enhancement with decreasing temperature, as is also the case for water from molecular dynamics simulations under ambient conditions. Based on X-ray emission spectroscopy and X-ray Raman scattering data we propose that the density difference contrast in SAXS is due to fluctuations between tetrahedral-like and hydrogen-bond distorted structures related to, respectively, low and high density water. We combine our experimental observations to propose a model of water as a temperature-dependent, fluctuating equilibrium between the two types of local structures driven by incommensurate requirements for minimizing enthalpy (strong near-tetrahedral hydrogen-bonds) and maximizing entropy (nondirectional H-bonds and disorder). The present results provide experimental evidence that the extreme differences anticipated in the hydrogen-bonding environment in the deeply supercooled regime surprisingly remain in bulk water even at conditions ranging from ambient up to close to the boiling point.

  • 28. Huang, Congcong
    et al.
    Wikfeldt, Kjartan Thor
    Stockholm University, Faculty of Science, Department of Physics.
    Tokushima, Takashi
    Nordlund, Dennis
    Harada, Yoshi
    Bergmann, Uwe
    Niebuhr, M.
    Weiss, T. M.
    Horikawa, Y.
    Leetmaa, Mikael
    Stockholm University, Faculty of Science, Department of Physics.
    Ljungberg, Mathias P.
    Stockholm University, Faculty of Science, Department of Physics.
    Takahashi, Osamu
    Lentz, Annika
    Ojamäe, Lars
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Shin, Shik
    Pettersson, Lars G.M.
    Stockholm University, Faculty of Science, Department of Physics.
    Nilsson, Anders
    Stockholm University, Faculty of Science, Department of Physics.
    Reply to Soper "Fluctuations in water around a bimodal distribution of local hydrogen bonded structural motifs"2010In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 107, no 12, article id E45Article in journal (Refereed)
  • 29.
    Högberg, Carl-Johan
    et al.
    Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry. Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry, Physical Chemistry.
    Lyubartsev, Alexander
    Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry, Physical Chemistry.
    Effect of Local Anesthetic Lidocaine on Electrostatic Properties of a Lipid Bilayer2008In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 94, p. 525-531Article in journal (Refereed)
    Abstract [en]

    The influence of local anesthetic lidocaine on electrostatic properties of a lipid membrane bilayer was studied by molecular dynamics simulations. The electrostatic dipole potential, charge densities, and orientations of the headgroup angle have been examined in presence of different amounts of charged or uncharged forms of lidocaine. Important differences of the membrane properties caused by the presence of the both forms of lidocaine are presented and discussed. Our simulations have shown that both charged and uncharged lidocaine cause almost the same increase of the dipole electrostatic potential in the middle of membrane though for different reasons. The increase, being about 90 mV for 9 mol % of lidocaine and 220 mV for 28 mol% of lidocaine, is of the size which may affect the functioning of voltage-gated ion channels.

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  • 30.
    Högberg, Carl-Johan
    et al.
    Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry, Physical Chemistry.
    Nikitin, Alexei
    Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry, Physical Chemistry.
    Lyubartsev, Alexander
    Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry, Physical Chemistry.
    Modification of the CHARMM force field for DMPC lipid bilayer2008In: Journal of Computational Chemistry, ISSN 0192-8651, E-ISSN 1096-987X, Vol. 29, no 14, p. 2359-2369Article in journal (Refereed)
    Abstract [en]

    The CHARMM force field for DMPC lipids was modified in order to improve agreement with experiment for a number of important properties of hydrated lipid bilayer. The modification consists in introduction of a scaling factor 0.83 for 1-4 electrostatic interactions (between atoms separated by three covalent bonds), which provides correct transgauche ratio in the alkane tails, and recalculation of the headgroup charges on the basis of HF/6-311(d,p) ab-initio computations. Both rigid TIP3P and flexible SPC water models were used with the new lipid model, showing similar results. The new model in a 75 ns simulation has shown a correct value of the area per lipid at zero surface tension, as well as good agreement with the experiment for the electron density, structure factor, and order parameters, including those in the headgroup part of lipids.

  • 31.
    Ivanov, Mikhail
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Atomistic Molecular Dynamics Simulations of Lipids Near TiO2 Nanosurfaces2021In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 125, no 29, p. 8048-8059Article in journal (Refereed)
    Abstract [en]

    Understanding of interactions between inorganic nanomaterials and biomolecules, and particularly lipid bilayers, is crucial in many biotechnological and biomedical applications, as well as for the evaluation of possible toxic effects caused by nanoparticles. Here, we present a molecular dynamics study of adsorption of two important constituents of the cell membranes, 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE), lipids to a number of titanium dioxide planar surfaces, and a spherical nanoparticle under physiological conditions. By constructing the number density profiles of the lipid headgroup atoms, we have identified several possible binding modes and calculated their relative prevalence in the simulated systems. Our estimates of the adsorption strength, based on the total fraction of adsorbed lipids, show that POPE binds to the selected titanium dioxide surfaces stronger than DMPC, due to the ethanolamine group forming hydrogen bonds with the surface. Moreover, while POPE shows a clear preference toward anatase surfaces over rutile, DMPC has a particularly high affinity to rutile(101) and a lower affinity to other surfaces. Finally, we study how lipid concentration, addition of cholesterol, as well as titanium dioxide surface curvature may affect overall adsorption.

  • 32.
    Ivanov, Mikhail
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Development of a bottom-up coarse-grained model for interactions of lipids with TiO2 nanoparticles2024In: Journal of Computational Chemistry, ISSN 0192-8651, E-ISSN 1096-987X, Vol. 45, no 16, p. 1364-1379Article in journal (Refereed)
    Abstract [en]

    Understanding interactions of inorganic nanoparticles with biomolecules is important in many biotechnology, nanomedicine, and toxicological research, however, the size of typical nanoparticles makes their direct modeling by atomistic simulations unfeasible. Here, we present a bottom-up coarse-graining approach for modeling titanium dioxide (TiO2) nanomaterials in contact with phospholipids that uses the inverse Monte Carlo method to optimize the effective interactions from the structural data obtained in small-scale all-atom simulations of TiO2 surfaces with lipids in aqueous solution. The resulting coarse-grained models are able to accurately reproduce the structural details of lipid adsorption on different titania surfaces without the use of an explicit solvent, enabling significant computational resource savings and favorable scaling. Our coarse-grained simulations show that small spherical TiO2 nanoparticles (𝑟=2 nm) can only be partially wrapped by a lipid bilayer with phosphoethanolamine headgroups, however, the lipid adsorption increases with the radius of the nanoparticle. The current approach can be used to study the effect of the size and shape of TiO2 nanoparticles on their interactions with cell membrane lipids, which can be a determining factor in membrane wrapping as well as the recently discovered phenomenon of nanoquarantining, which involves the formation of layered nanomaterial–lipid structures.

  • 33.
    Ivanov, Mikhail
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Posysoev, Maksim
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK). Stockholm University, Science for Life Laboratory (SciLifeLab).
    Coarse-Grained Modeling Using Neural Networks Trained on Structural Data2023In: Journal of Chemical Theory and Computation, ISSN 1549-9618, E-ISSN 1549-9626, Vol. 19, no 19, p. 6704-6717Article in journal (Refereed)
    Abstract [en]

    We propose a method of bottom-up coarse-graining, in which interactions within a coarse-grained model are determined by an artificial neural network trained on structural data obtained from multiple atomistic simulations. The method uses ideas of the inverse Monte Carlo approach, relating changes in the neural network weights with changes in average structural properties, such as radial distribution functions. As a proof of concept, we demonstrate the method on a system interacting by a Lennard-Jones potential modeled by a simple linear network and a single-site coarse-grained model of methanol-water solutions. In the latter case, we implement a nonlinear neural network with intermediate layers trained by atomistic simulations carried out at different methanol concentrations. We show that such a network acts as a transferable potential at the coarse-grained resolution for a wide range of methanol concentrations, including those not included in the training set.

  • 34.
    Ivanov, Sergei
    et al.
    Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry.
    Lyubartsev, Alexander
    Bead-Fourier path integral molecular dynamics for identical particles2005In: Journal of Chemical Physics, ISSN 0021-9606, E-ISSN 1089-7690, Vol. 123, p. 034105-Article in journal (Other academic)
    Abstract [en]

    The Bead-Fourier path integral molecular dynamics technique introduced earlier [ S. D. Ivanov, A. P. Lyubartsev, and A. Laaksonen, Phys. Rev. E 67 066710 (2003) ] is applied for simulation of electrons in the simplest molecules: molecular hydrogen, helium atom, and their ions. Special attention is paid to the correct description of electrons in the core region of a nucleus. In an attempt to smooth the Coulomb potential at small distances, a recipe is suggested. The simulation results are in excellent agreement with the analytical solution for the “harmonic helium atom”, as well as with the vibrational potential of the H2 molecule and He ionization energies. It is demonstrated, that the Bead-Fourier path integral molecular dynamics technique is able to provide the accuracy required for the description of electron structure and chemical bonds in cases when electron exchange effects need not be taken into account.

  • 35. Jesudason, C.G.
    et al.
    Lyubartsev, Alexander
    Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry.
    Laaksonen, Aatto
    Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry.
    Conformational characteristics of single flexible polyelectrolyte chain2009In: The European Physical Journal E Soft matter, ISSN 1292-8941, E-ISSN 1292-895X, Vol. 30, p. 341-350Article in journal (Refereed)
    Abstract [en]

    The behavior of a flexible anionic chain of 150 univalent and negatively charged beads connected by harmonic-like potential interactions with each other in the presence of equal number of positive and free counterions, observed in molecular dynamics simulations with Langevin thermostat, is described in a temperature range from 0.1 to 10.0 in reduced units. The total and Coulombic energies, radial distribution functions, radii of gyration, end-to-end distances of the chain are depicted. Our results turned out to be qualitatively similar to the results obtained earlier for a lattice polyelectrolyte model, including temperature maximum of the polyelectrolyte chain and internal phase transition which seems to occur abruptly at low temperatures for all the systems studied, judging from the shape of end-to end distance, gyration radius and energy profiles.

  • 36.
    Jämbeck, Joakim P. M.
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Eriksson, Emma S. E.
    Laaksonen, Aatto
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Eriksson, Leif A.
    Molecular Dynamics Studies of Liposomes as Carriers for Photosensitizing Drugs: Development, Validation, and Simulations with a Coarse-Grained Model2014In: Journal of Chemical Theory and Computation, ISSN 1549-9618, E-ISSN 1549-9626, Vol. 10, no 1, p. 5-13Article in journal (Refereed)
    Abstract [en]

    Liposomes are proposed as drug delivery systems and can in principle be designed so as to cohere with specific tissue types or local environments. However, little detail is known about the exact mechanisms for drug delivery and the distributions of drug molecules inside the lipid carrier. In the current work, a coarse-grained (CG) liposome model is developed, consisting of over 2500 lipids, with varying degrees of drug loading. For the drug molecule, we chose hypericin, a natural compound proposed for use in photodynamic therapy, for which a CG model was derived and benchmarked against corresponding atomistic membrane bilayer model simulations. Liposomes with 21-84 hypericin molecules were generated and subjected to 10 microsecond simulations. Distribution of the hypericins, their orientations within the lipid bilayer, and the potential of mean force for transferring a hypericin molecule from the interior aqueous droplet through the liposome bilayer are reported herein.

  • 37.
    Jämbeck, Joakim P. M.
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    An extension and further validation of an all atomistic force field for biological membranes2012In: Journal of Chemical Theory and Computation, ISSN 1549-9618, E-ISSN 1549-9626, Vol. 8, no 8, p. 2938-2948Article in journal (Refereed)
    Abstract [en]

    Biological membranes are versatile in composition and host intriguing molecular processes. In order to be able to study these systems, an accurate model Hamiltonian or force field (FF) is a necessity. Here, we report the results of our extension of earlier developed all-atomistic FF parameters for fully saturated phospholipids that complements an earlier parameter set for saturated phosphatidylcholine lipids (J. Phys. Chem. B, 2012, 116, 3164-3179). The FF, coined Slipids (Stockholm lipids), now also includes parameters for unsaturated phosphatidylcholine and phosphatidylethanolamine lipids, e.g., POPC, DOPC, SOPC, POPE, and DOPE. As the extended set of parameters is derived with the same philosophy as previously applied, the resulting FF has been developed in a fully consistent manner. The capabilities of Slipids are demonstrated by performing long simulations without applying any surface tension and using the correct isothermal-isobaric (NPT) ensemble for a range of temperatures and carefully comparing a number of properties with experimental findings. Results show that several structural properties are very well reproduced, such as scattering form factors, NMR order parameters, thicknesses, and area per lipid. Thermal dependencies of different thicknesses and area per lipid are reproduced as well Lipid diffusion is systematically slightly underestimated, whereas the normalized lipid diffusion follows the experimental trends. This is believed to be due to the lack of collective movement in the relatively small bilayer patches used Furthermore, the compatibility with amino acid FFs from the AMBER family is tested in explicit transmembrane complexes of the WALP23 peptide with DLPC and DOPC bilayers, and this shows that Slipids can be used to study more complex and biologically relevant systems.

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  • 38.
    Jämbeck, Joakim P. M.
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Another piece of the membrane puzzle: extending slipids further2013In: Journal of Chemical Theory and Computation, ISSN 1549-9618, E-ISSN 1549-9626, Vol. 9, no 1, p. 774-784Article in journal (Refereed)
    Abstract [en]

    To be able to model complex biological membranes in a more realistic manner, the force field Slipids (Stockholm lipids) has been extended to include parameters for sphingomyelin (SM), phosphatidylglycerol (PG), phosphatidylserine (PS) lipids, and cholesterol. Since the parametrization scheme was faithful to the scheme used in previous editions of Slipids, all parameters are consistent and fully compatible. The results of careful validation of a number of key structural properties for one and two component lipid bilayers are in excellent agreement with experiments. Potentials of mean force for transferring water across binary mixtures of lipids and cholesterol were also computed in order to compare water permeability rates to experiments. In agreement with experimental and simulation studies, it was found that the permeability and partitioning of water is affected by cholesterol in lipid bilayers made of saturated lipids to the largest extent. With the extensions of Slipids presented here, it is now possible to study complex systems containing many different lipids and proteins in a fully atomistic resolution in the isothermic-isobaric (NPT) ensemble, which is the proper ensemble for membrane simulations.

  • 39.
    Jämbeck, Joakim P. M.
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Derivation and Systematic Validation of a Refined All-Atom Force Field for Phosphatidylcholine Lipids2012In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 116, no 10, p. 3164-3179Article in journal (Refereed)
    Abstract [en]

    An all-atomistic force field (FF) has been developed for fully saturated phospholipids. The parametrization has been largely based on high-level ab initio calculations in order to keep the empirical input to a minimum. Parameters for the lipid chains have been developed based on knowledge about bulk alkane liquids, for which thermodynamic and dynamic data are excellently reproduced. The FFs ability to simulate lipid bilayers in the liquid crystalline phase in a tensionless ensemble was tested in simulations of three lipids: 1,2-diauroyl-sn-glycero-3-phospocholine (DLPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and 1,2-dipalmitoyl-sn-glycero-3-phospcholine (DPPC). Computed areas and volumes per lipid, and three different kinds of bilayer thicknesses, have been investigated. Most importantly NMR order parameters and scattering form factors agree in an excellent manner with experimental data under a range of temperatures. Further, the compatibility with the AMBER FF for biomolecules as well as the ability to simulate bilayers in gel phase was demonstrated. Overall, the FF presented here provides the important balance between the hydrophilic and hydrophobic forces present in lipid bilayers and therefore can be used for more complicated studies of realistic biological membranes with protein insertions.

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  • 40.
    Jämbeck, Joakim P. M.
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Exploring the Free Energy Landscape of Solutes Embedded in Lipid Bilayers2013In: The Journal of Physical Chemistry Letters, E-ISSN 1948-7185, Vol. 4, no 11, p. 1781-1787Article in journal (Refereed)
    Abstract [en]

    Free energy calculations are vital for our understanding of biological processes on an atomistic scale and can offer insight to various mechanisms. However, in some cases, degrees of freedom (DOFs) orthogonal to the reaction coordinate have high energy barriers and/or long equilibration times, which prohibit proper sampling. Here we identify these orthogonal DOFs when studying the transfer of a solute from water to a model membrane. Important DOFs are identified in bulk liquids of different dielectric nature with metadynamics simulations and are used as reaction coordinates for the translocation process, resulting in two- and three-dimensional space of reaction coordinates. The results are in good agreement with experiments and elucidate the pitfalls of using one-dimensional reaction coordinates. The calculations performed here offer the most detailed free energy landscape of solutes embedded in lipid bilayers to date and show that free energy calculations can be used to study complex membrane translocation phenomena.

  • 41.
    Jämbeck, Joakim P. M.
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Implicit inclusion of atomic polarization in modeling of partitioning between water and lipid bilayers2013In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 15, no 13, p. 4677-4686Article in journal (Refereed)
    Abstract [en]

    We propose an effective and straightforward way of including atomic polarization in simulations of the partitioning of small molecules in inhomogenous media based on classical molecular dynamics with non-polarizable force fields. The approach presented here takes advantage of the relatively fast sampling of phase space obtained with additive force fields by adding the polarization effects afterwards. By using pre-polarized charges for the polar and non-polar phases together with a polarization correction term the effects of atomic polarization are effectively taken into account. The results show a clear improvement compared to using the more common setup with one set of charges obtained from gas phase ab initio calculations. It is shown that when proper measures are taken into account computer simulations with non-polarizable force fields are able to accurately determine water-membrane partitioning and preferential location of small molecules in the membrane interior. We believe that the approach presented here can be useful in rational drug design and in investigations of molecular mechanisms of anesthetic or toxic action.

  • 42.
    Jämbeck, Joakim P. M.
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Update to the General Amber Force Field for Small Solutes with an Emphasis on Free Energies of Hydration2014In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 118, no 14, p. 3793-3804Article in journal (Refereed)
    Abstract [en]

    An approach to a straightforward reparametrization of the general AMBER force field (GAFF) for small organic solutes and druglike compounds is presented. The parametrization is based on specific pair interactions between the solvent and the solute, namely, the interactions between the constituting atoms of the solute and the oxygen of water were tuned in order to reproduce experimental hydration free energies for small model compounds. The key of the parametrization was to abandon the Lorentz-Berthelot combination rules for the van der Waals interactions. These parameters were then used for larger solutes in order to validate the newly derived pair interactions. In total close to 600 hydration free energies are computed, ranging from simple alkanes to multifunctional drug compounds, and compared to experimental data. The results show that the proposed parameters work well in describing the interactions between the solute and the solvent and that the agreement in absolute numbers is good. This modified version of GAFF is a good candidate for computing and predicting hydration free energies on a large scale, which has been a long-sought goal of computational chemists and can be used in rational drug design.

  • 43.
    Jämbeck, Joakim P. M.
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Mocci, Francesca
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Laaksonen, Aatto
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Partial Atomic Charges and Their Impact on the Free Energy of Solvation2013In: Journal of Computational Chemistry, ISSN 0192-8651, E-ISSN 1096-987X, Vol. 34, no 3, p. 187-197Article in journal (Refereed)
    Abstract [en]

    Free energies of solvation (Delta G) in water and n-octanol have been computed for common drug molecules by molecular dynamics simulations with an additive fixed-charge force field. The impact of the electrostatic interactions was investigated by computing the partial atomic charges with four methods that all fit the charges from the quantum mechanically determined electrostatic potential (ESP). Due to the redistribution of electron density that occurs when molecules are transferred from gas phase to condensed phase, the polarization impact was also investigated. By computing the partial atomic charges with the solutes placed in a conductor-like continuum, the charges were effectively polarized to take the polarization effects into account. No polarization correction term or similar was considered, only the partial atomic charges. Results show that free energies are very sensitive to the choice of atomic charges and that Delta G can differ by several k(B)T depending on the charge computing method. Inclusion of polarization effects makes the solutes too hydrophilic with most methods and in vacuo charges make the solutes too hydrophobic. The restrained-ESP methods together with effectively polarized charges perform well in our test set and also when applied to a larger set of molecules. The effect of water models is also highlighted and shows that the conclusions drawn are valid for different three-point models. Partitioning between an aqueous and a hydrophobic phase is also described better if the two environment's polarization is taken into account, but again the results are sensitive to the charge calculation method. Overall, the results presented here show that effectively polarized charges can improve the description of solvating a drug-like molecule in a solvent and that the choice of partial atomic charges is crucial to ensure that molecular simulations produce reliable results.

  • 44. Kokot, Hana
    et al.
    Kokot, Boštjan
    Sebastijanović, Aleksandar
    Voss, Carola
    Podlipec, Rok
    Zawilska, Patrycja
    Berthing, Trine
    Ballester‐López, Carolina
    Høgh Danielsen, Pernille
    Contini, Claudia
    Ivanov, Mikhail
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Krišelj, Ana
    Čotar, Petra
    Zhou, Qiaoxia
    Ponti, Jessica
    Zhernovkov, Vadim
    Schneemilch, Matthew
    Doumandji, Zahra
    Pušnik, Mojca
    Umek, Polona
    Pajk, Stane
    Joubert, Olivier
    Schmid, Otmar
    Urbančič, Iztok
    Irmler, Martin
    Beckers, Johannes
    Lobaskin, Vladimir
    Halappanavar, Sabina
    Quirke, Nick
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Vogel, Ulla
    Koklič, Tilen
    Stoeger, Tobias
    Štrancar, Janez
    Prediction of Chronic Inflammation for Inhaled Particles: the Impact of Material Cycling and Quarantining in the Lung Epithelium2020In: Advanced Materials, ISSN 0935-9648, E-ISSN 1521-4095, Vol. 32, no 47, article id 2003913Article in journal (Refereed)
    Abstract [en]

    On a daily basis, people are exposed to a multitude of health-hazardous airborne particulate matter with notable deposition in the fragile alveolar region of the lungs. Hence, there is a great need for identification and prediction of material-associated diseases, currently hindered due to the lack of in-depth understanding of causal relationships, in particular between acute exposures and chronic symptoms. By applying advanced microscopies and omics to in vitro and in vivo systems, together with in silico molecular modeling, it is determined herein that the long-lasting response to a single exposure can originate from the interplay between the newly discovered nanomaterial quarantining and nanomaterial cycling between different lung cell types. This new insight finally allows prediction of the spectrum of lung inflammation associated with materials of interest using only in vitro measurements and in silico modeling, potentially relating outcomes to material properties for a large number of materials, and thus boosting safe-by-design-based material development. Because of its profound implications for animal-free predictive toxicology, this work paves the way to a more efficient and hazard-free introduction of numerous new advanced materials into our lives. 

  • 45. Koppisetty, Chaitanya A. K.
    et al.
    Frank, Martin
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Nyholm, Per-Georg
    Binding energy calculations for hevein-carbohydrate interactions using expanded ensemble molecular dynamics simulations2015In: Journal of Computer-Aided Molecular Design, ISSN 0920-654X, E-ISSN 1573-4951, Vol. 29, no 1, p. 13-21Article in journal (Refereed)
    Abstract [en]

    Accurate estimation of protein-carbohydrate binding energies using computational methods is a challenging task. Here we report the use of expanded ensemble molecular dynamics (EEMD) simulation with double decoupling for estimation of binding energies of hevein, a plant lectin with its monosaccharide and disaccharide ligands GlcNAc and (GlcNAc)(2), respectively. In addition to the binding energies, enthalpy and entropy components of the binding energy are also calculated. The estimated binding energies for the hevein-carbohydrate interactions are within the range of +/- 0.5 kcal of the previously reported experimental binding data. For comparison, binding energies were also estimated using thermodynamic integration, molecular dynamics end point calculations (MM/GBSA) and the expanded ensemble methodology is seen to be more accurate. To our knowledge, the method of EEMD simulations has not been previously reported for estimating biomolecular binding energies.

  • 46.
    Korolev, Nikolai
    et al.
    Nanyang Technological University, Singapore.
    Allahverdi, Abdollah
    Nanyang Technological University, Singapore.
    Yang, Ye
    Nanyang Technological University, Singapore.
    Fan, Yanping
    Nanyang Technological University, Singapore.
    Lyubartsev, Alexander
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Nordenskiöld, Lars
    Nanyang Technological University, Singapore.
    Electrostatic Origin of Salt-induced Nucleosome Array Compaction2010In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 99, p. 1896-1905Article in journal (Refereed)
    Abstract [en]

    The physical mechanism of the folding and unfolding of chromatin is fundamentally related to transcription but is incompletely characterized and not fully understood. We experimentally and theoretically studied chromatin compaction by investigating the salt-mediated folding of an array made of 12 positioning nucleosomes with 177 bp repeat length. Sedimentation velocity measurements were performed to monitor the folding provoked by addition of cations Na+, K+, Mg2+, Ca2+, spermidine3+, Co(NH3)63+, and spermine4+. We found typical polyelectrolyte behavior, with the critical concentration of cation needed to bring about maximal folding covering a range of almost five orders of magnitude (from 2 μM for spermine4+ to 100 mM for Na+). A coarse-grained model of the nucleosome array based on a continuum dielectric description and including the explicit presence of mobile ions and charged flexible histone tails was used in computer simulations to investigate the cation-mediated compaction. The results of the simulations with explicit ions are in general agreement with the experimental data, whereas simple Debye-Hückel models are intrinsically incapable of describing chromatin array folding by multivalent cations. We conclude that the theoretical description of the salt-induced chromatin folding must incorporate explicit mobile ions that include ion correlation and ion competition effects.

  • 47.
    Korolev, Nikolai
    et al.
    Nanyang Technological University, Singapore.
    Lyubartsev, Alexander
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Nordenskiöld, Lars
    Nanyang Technological University, Singapore.
    Cation-indiced polyelectrolyte-polyelectrolyte attraction in solutions of DNA and nucleosome core particles2010In: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 158, p. 32-47Article in journal (Refereed)
    Abstract [en]

    The paper reviews our current studies on the experimentally induced cation compaction and aggregation in solutions of DNA and nucleosome core particles and the theoretical modelling of these processes using coarse-grained continuum models with explicit mobile ions and with all-atom molecular dynamics (MD) simulations. Recent experimental results on DNA condensation by cationic oligopeptides and the effects of added salt are presented. The results of MD simulations modelling DNA–DNA attraction due to the presence of multivalent ions including the polyamine spermidine and fragments of histone tails, which exhibit bridging between adjacent DNA molecules, are discussed. Experimental data on NCP aggregation, using recombinantly prepared systems are summarized. Literature data and our results of studying of the NCP solutions are compared with predictions of coarse-grained MD simulations, including the important ion correlation as well as bridging mechanisms. The importance of the results to chromatin folding and aggregation is discussed.

  • 48. Korolev, Nikolay
    et al.
    Allahverdi, Abdollah
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Nordenskioeld, Lars
    The polyelectrolyte properties of chromatin2012In: Soft Matter, ISSN 1744-683X, E-ISSN 1744-6848, Vol. 8, no 36, p. 9322-9333Article, review/survey (Refereed)
    Abstract [en]

    Double helical DNA is a negatively charged polyelectrolyte and exists in the nucleus of living cells as chromatin, a highly compacted but dynamic complex with histone proteins. The first level of DNA compaction is the linear array of the nucleosome core particles (NCP), which is a well-defined structure of 145-147 bp DNA with the histone octamer, connected by linker DNA. Higher levels of chromatin compaction include two routes which may overlap: intramolecular folding of the nucleosome array resulting in formation of the 30 nm fibre and intermolecular aggregation (self-association) between different arrays (or distant fibres of the same chromosome). This review describes how the polyelectrolyte properties of chromatin are illustrated by experimental results of folding and self-association of well-defined model chromatin, in the form of recombinant nucleosome arrays, and how these properties can be understood from computer modelling. Chromatin compaction shows considerable similarities to DNA condensation. However, the structure of condensed chromatin is sensitive to the detailed molecular features of the nucleosome-nucleosome interactions which include the influence of the histone tails and their modifications.

  • 49. Korolev, Nikolay
    et al.
    Fan, Yanping
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Nordenskioeld, Lars
    Modelling chromatin structure and dynamics: status and prospects2012In: Current opinion in structural biology, ISSN 0959-440X, E-ISSN 1879-033X, Vol. 22, no 2, p. 151-159Article in journal (Refereed)
    Abstract [en]

    The packaging of genomic DNA into chromatin in the eukaryotic cell nucleus demands extensive compaction. This requires attractive nucleosome-nucleosome interactions to overcome repulsion between the negatively charged DNA segments as well as other constraints. At the same time, DNA must be dynamically accessible to the cellular machinery that operates on it. Recent progress in the experimental characterisation of the higher order structure and dynamics of well-defined chromatin fibres has stimulated the attempts at theoretical description of chromatin and the nucleosome. Here we review the present status of chromatin Modelling, with particular emphasis on coarse-grained computer simulation models, the role of electrostatic interactions, and discuss future perspectives in the field.

  • 50. Korolev, Nikolay
    et al.
    Luo, Di
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Nordenskiöld, Lars
    A Coarse-Grained DNA Model Parameterized from Atomistic Simulations by Inverse Monte Carlo2014In: Polymers, E-ISSN 2073-4360, Vol. 6, no 6, p. 1655-1675Article in journal (Refereed)
    Abstract [en]

    Computer modeling of very large biomolecular systems, such as long DNA polyelectrolytes or protein-DNA complex-like chromatin cannot reach all-atom resolution in a foreseeable future and this necessitates the development of coarse-grained (CG) approximations. DNA is both highly charged and mechanically rigid semi-flexible polymer and adequate DNA modeling requires a correct description of both its structural stiffness and salt-dependent electrostatic forces. Here, we present a novel CG model of DNA that approximates the DNA polymer as a chain of 5-bead units. Each unit represents two DNA base pairs with one central bead for bases and pentose moieties and four others for phosphate groups. Charges, intra-and inter-molecular force field potentials for the CG DNA model were calculated using the inverse Monte Carlo method from all atom molecular dynamic (MD) simulations of 22 bp DNA oligonucleotides. The CG model was tested by performing dielectric continuum Langevin MD simulations of a 200 bp double helix DNA in solutions of monovalent salt with explicit ions. Excellent agreement with experimental data was obtained for the dependence of the DNA persistent length on salt concentration in the range 0.1-100 mM. The new CG DNA model is suitable for modeling various biomolecular systems with adequate description of electrostatic and mechanical properties.

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