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  • 1.
    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, 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.

  • 2. 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, 1181-1188 p.Article 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.

  • 3.
    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, 13385-13398 p.Article 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.

  • 4.
    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, 18126-18139 p.Article 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.

  • 5.
    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, 18110-18125 p.Article 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.

  • 6.
    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, 10013-10020 p.Article 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.

  • 7. 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, 14572-14581 p.Article 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.

  • 8.
    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, 12826-12842 p.Article 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.

  • 9.
    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, 28263-28274 p.Article 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.

  • 10. 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, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 2, 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.

  • 11.
    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, 953-960 p.Article 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.

  • 12. 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, 15214-15218 p.Article 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.

  • 13.
    Huang, Congcong
    et al.
    Stanford.
    Wikfeldt, Kjartan Thor
    Stockholm University, Faculty of Science, Department of Physics.
    Tokushima, Takashi
    SPring-8.
    Nordlund, Dennis
    Stanford.
    Harada, Yoshi
    Bergmann, Uwe
    Stanford.
    Niebuhr, M.
    Stanford.
    Weiss, T.M.
    Stanford.
    Horikawa, Y.
    SPring-8.
    Leetmaa, Mikael
    Stockholm University, Faculty of Science, Department of Physics.
    Ljungberg, Mathias P.
    Stockholm University, Faculty of Science, Department of Physics.
    Takahashi, Osamu
    University of Hiroshima.
    Lentz, Annika
    Linköpings Universitet.
    Ojamäe, Lars
    Linköpings Universitet.
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Shin, Shik
    Tokyo University.
    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, E45- p.Article in journal (Refereed)
  • 14.
    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, 525-531 p.Article 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.

  • 15.
    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, 2359-2369 p.Article 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.

  • 16.
    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, 034105- p.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.

  • 17. 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, 341-350 p.Article 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.

  • 18.
    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, 5-13 p.Article 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.

  • 19.
    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, 2938-2948 p.Article 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.

  • 20.
    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, 774-784 p.Article 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.

  • 21.
    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, 3164-3179 p.Article 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.

  • 22.
    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: Journal of Physical Chemistry Letters, ISSN 1948-7185, E-ISSN 1948-7185, Vol. 4, no 11, 1781-1787 p.Article 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.

  • 23.
    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, 4677-4686 p.Article 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.

  • 24.
    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, 3793-3804 p.Article 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.

  • 25.
    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, 187-197 p.Article 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.

  • 26. 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, 13-21 p.Article 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.

  • 27.
    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, 1896-1905 p.Article 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.

  • 28.
    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, 32-47 p.Article 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.

  • 29. 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, 9322-9333 p.Article, 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.

  • 30. 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, 151-159 p.Article 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.

  • 31. 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, ISSN 2073-4360, E-ISSN 2073-4360, Vol. 6, no 6, 1655-1675 p.Article 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.

  • 32. Korolev, Nikolay
    et al.
    Nordenskiöld, Lars
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Multiscale coarse-grained modelling of chromatin components: DNA and the nucleosome2016In: Advances in Colloid and Interface Science, ISSN 0001-8686, E-ISSN 1873-3727, Vol. 232, 36-48 p.Article in journal (Refereed)
    Abstract [en]

    To model large biomolecular systems, such as cell and organelles an atomistic description is not currently achievable and is not generally practical. Therefore, simplified coarse-grained (CG) modelling becomes a necessity. One of the most important cellular components is chromatin, a large DNA-protein complex where DNA is highly compacted. Recent progress in coarse graining modelling of the major chromatin components, double helical DNA and the nucleosome core particle (NCP) is presented. First, general principles and approaches allowing rigorous bottom-to-top generation of interaction potentials in the CG models are presented. Then, recent CG models of DNA are reviewed and their adequacy is benchmarked against experimental data on the salt dependence of DNA flexibility (persistence length). Furthermore, a few recent CG models of the NCP are described and their application for studying salt-dependent NCP-NCP interaction is discussed. An example of a multiscale approach to CG modelling of chromatin is presented where interactions and self-assembly of thousands of NCPs in solution are observed.

  • 33. Korolev, Nikolay
    et al.
    Yu, Hang
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Nordenskiöld, Lars
    Molecular Dynamics Simulations Demonstrate the Regulation of DNA-DNA Attraction by H4 Histone Tail Acetylations and Mutations2014In: Biopolymers, ISSN 0006-3525, E-ISSN 1097-0282, Vol. 101, no 10, 1051-1064 p.Article in journal (Refereed)
    Abstract [en]

    The positively charged N-terminal histone tails play a crucial role in chromatin compaction and are important modulators of DNA transcription, recombination, and repair. The detailed mechanism of the interaction of histone tails with DNA remains elusive. To model the unspecific interaction of histone tails with DNA, all-atom molecular dynamics (MD) simulations were carried out for systems of four DNA 22-mers in the presence of 20 or 16 short fragments of the H4 histone tail (variations of the 16-23 a. a. KRHRKVLR sequence, as well as the unmodified fragment a. a. 13-20, GGAKRHRK). This setup with high DNA concentration, explicit presence of DNA-DNA contacts, presence of unstructured cationic peptides (histone tails) and K+ mimics the conditions of eukaryotic chromatin. A detailed account of the DNA interactions with the histone tail fragments, K+ and water is presented. Furthermore, DNA structure and dynamics and its interplay with the histone tail fragments binding are analysed. The charged side chains of the lysines and arginines play major roles in the tailmediated DNA-DNA attraction by forming bridges and by coordinating to the phosphate groups and to the electronegative sites in the minor groove. Binding of all species to DNA is dynamic. The structure of the unmodified fully-charged H4 16-23 a. a. fragment KRHRKVLR is dominated by a stretched conformation. The H4 tail a. a. fragment GGAKRHRK as well as the H4 Lys16 acetylated fragment are highly flexible. The present work allows capturing typical features of the histone tail-counterionDNA structure, interaction and dynamics.

  • 34.
    Laaksonen, Aatto
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Lyubartsev, Alexander
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Mocci, Francesca
    Cagliary University, Italy.
    M.DynaMix Studies of Solvation, Solubility and Permeability2012In: Molecular Dynamics - Studies of Synthetic and Biological Macromolecules / [ed] Lichang Wang, InTech, 2012, 85-106 p.Chapter in book (Refereed)
  • 35.
    Leetmaa, Mikael
    et al.
    Stockholm University, Faculty of Science, Department of Physics.
    Ljungberg, Mathias
    Stockholm University, Faculty of Science, Department of Physics.
    Lyubartsev, Alexander
    Stockholm University, Faculty of Science, Department of Physics.
    Nilsson, Anders
    Stockholm University, Faculty of Science, Department of Physics.
    Pettersson, Lars G.M.
    Stockholm University, Faculty of Science, Department of Physics.
    Theoretical Approximations to X-ray Absorption Spectroscopy of Liquid Water and Ice2010In: Journal of Electron Spectroscopy and Related Phenomena, ISSN 0368-2048, E-ISSN 1873-2526, Vol. 177, no 2-3, 135-157 p.Article in journal (Refereed)
    Abstract [en]

    We review methods to compute x-ray absorption spectra (XAS) with special focus on the transition potential approach of Triguero et al. [Phys. Rev. B 58, 8097 (1998)] and its application to calculations on water in condensed phase. We discuss the absolute energy scale, functional dependence, broadening versus sampling of intra- and intermolecular vibrational modes, treatment of the continuum, cluster size convergence as well as compare with periodic calculations and with experiment; periodic and cluster model calculations are found to agree very closely in the relevant near-edge region although neither reproduces the pre-edge and main-edge features in the experimental spectra of thin ice films. The real space grid representation of the wave function in the periodic calculations allows a more extended energy range to be described and we find satisfactory agreement with experiment for higher energy continuum resonances. Two proposed alternative approaches using either the potential from a full core-hole (FCH) or the full core-hole with an excited electron in the lowest state (XCH) are shown to lead to spectra that deviate significantly from experiment.

  • 36.
    Ljungberg, Mathias
    et al.
    Stockholm University, Faculty of Science, Department of Physics.
    Lyubartsev, Alexander
    Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry.
    Nilsson, Anders
    Stanford Synchrotron Radiation Lightsource.
    Pettersson, Lars
    Stockholm University, Faculty of Science, Department of Physics.
    Assessing the electric-field approximation to IR and Raman spectra of dilute HOD in D2O2009In: Journal of Chemical Physics, ISSN 0021-9606, E-ISSN 1089-7690, Vol. 131, 034501- p.Article in journal (Refereed)
    Abstract [en]

    We analyze the validity of the commonly used electric-field (E-field) approximation to vibrational OH stretch Raman spectra of dilute HOD in D2O by computing the OH stretch frequency of all molecules in several different structure models, each containing around 2000 molecules. The calculations are done at the B3LYP level using clusters containing 32 molecules centered around the molecule for which the frequencies are calculated; the large cluster size is required due to significant nonlocal contributions influencing the computed frequencies. The vibrational frequencies are determined using a six-point potential optimized discrete variable representation. Raman and infrared intensities are furthermore computed to generate the spectra. We find that a quadratic fit of E-field versus frequency gives a reasonable representation of the calculated distribution of frequencies. However, the mapping depends significantly on the structural model and is thus not universal. Anharmonic couplings are calculated for several optimized clusters showing a general trend to compress the computed frequency distributions, which is in agreement with dynamical simulations (motional narrowing).

  • 37.
    Lyubartsev, Alexander
    et al.
    Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry.
    Ben-Naim, Arieh
    The Hebrew University of Jerusalem.
    One dimensional model for water and aqueous solutions. Part V. Monte Carlo simulation of dilute solutions of hard rod in waterlike particles2009In: Journal of Chemical Physics, ISSN 0021-9606, E-ISSN 1089-7690, Vol. 131, 204507- p.Article in journal (Refereed)
    Abstract [en]

    Wehave carried out Monte Carlo simulation on the primitive onedimensional model for water described earlier [A. Ben-Naim, J. Chem.Phys. 128, 024506 (2008)]. We show that by taking intoaccount second nearest neighbor interactions, one can obtain the characteristicanomalous solvation thermodynamic quantities of inert solutes in water. Thismodel clearly demonstrates the molecular origin of the large negativeentropy of solvation of an inert solute in water.

  • 38.
    Lyubartsev, Alexander
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Mirzoev, Alexander
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Chen, Li Jun
    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.
    Systematic coarse-graining of molecular models by the Newton inversion method2010In: Faraday discussions (Online), ISSN 1359-6640, E-ISSN 1364-5498, Vol. 144, 43-56 p.Article in journal (Refereed)
    Abstract [en]

    Systematic construction of coarse-grained molecular models from detailed atomistic simulations, and even from ab initio simulations is discussed. Atomistic simulations are first performed to extract structural information about the system, which is then used to determine effective potentials for a coarse-grained model of the same system. The statistical-mechanical equations expressing the canonical properties in terms of potential parameters can be inverted and solved numerically according to the iterative Newton scheme. In our previous applications, known as the Inverse Monte Carlo, radial distribution functions were inverted to reconstruct pair potential, while in a more general approach the targets can be other canonical averages. We have considered several examples of coarse-graining; for the united atom water model we suggest an easy way to overcome the known problem of high pressure. Further, we have developed coarse-grained models for L- and D-prolines, dissolved here in an organic solvent (dimethylsulfoxide), keeping their enantiomeric properties from the corresponding all-atom proline model. Finally, we have revisited the previously developed coarse-grained lipid model based on an updated all-atomic force field. We use this model in large-scale meso-scale simulations demonstrating spontaneous formation of different structures, such as vesicles, micelles, and multi-lamellar structures, depending on thermodynamical conditions.

  • 39.
    Lyubartsev, Alexander P.
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Korolev, Nikolay
    Fan, Yanping
    Nordenskiöld, Lars
    Multiscale modelling of nucleosome core particle aggregation2015In: Journal of Physics: Condensed Matter, ISSN 0953-8984, E-ISSN 1361-648X, Vol. 27, no 6, 064111Article in journal (Refereed)
    Abstract [en]

    The nucleosome core particle (NCP) is the basic building block of chromatin. Under the influence of multivalent cations, isolated mononucleosomes exhibit a rich phase behaviour forming various columnar phases with characteristic NCP-NCP stacking. NCP stacking is also a regular element of chromatin structure in vivo. Understanding the mechanism of nucleosome stacking and the conditions leading to self-assembly of NCPs is still incomplete. Due to the complexity of the system and the need to describe electrostatics properly by including the explicit mobile ions, novel modelling approaches based on coarse-grained (CG) methods at the multiscale level becomes a necessity. In this work we present a multiscale CG computer simulation approach to modelling interactions and self-assembly of solutions of NCPs induced by the presence of multivalent cations. Starting from continuum simulations including explicit three-valent cobalt(III) hexammine (CoHex(3+)) counterions and 20 NCPs, based on a previously developed advanced CG NCP model with one bead per amino acid and five beads per two DNA base pair unit (Fan et al 2013 PLoS One 8 e54228), we use the inverse Monte Carlo method to calculate effective interaction potentials for a 'super-CG' NCP model consisting of seven beads for each NCP. These interaction potentials are used in large-scale simulations of up to 5000 NCPs, modelling self-assembly induced by CoHex(3+). The systems of 'super-CG' NCPs form a single large cluster of stacked NCPs without long-range order in agreement with experimental data for NCPs precipitated by the three-valent polyamine, spermidine(3+).

  • 40.
    Lyubartsev, Alexander P.
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Naomé, Aymeric
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK). University of Namur, Belgium .
    Vercauteren, Daniel P.
    Laaksonen, Aatto
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK). Stockholm University, Science for Life Laboratory (SciLifeLab).
    Systematic hierarchical coarse-graining with the inverse Monte Carlo method2015In: Journal of Chemical Physics, ISSN 0021-9606, E-ISSN 1089-7690, Vol. 143, no 24, 243120Article in journal (Refereed)
    Abstract [en]

    We outline our coarse-graining strategy for linking micro-and mesoscales of soft matter and biological systems. The method is based on effective pairwise interaction potentials obtained in detailed ab initio or classical atomistic Molecular Dynamics (MD) simulations, which can be used in simulations at less accurate level after scaling up the size. The effective potentials are obtained by applying the inverse Monte Carlo (IMC) method [A. P. Lyubartsev and A. Laaksonen, Phys. Rev. E 52(4), 3730-3737 (1995)] on a chosen subset of degrees of freedom described in terms of radial distribution functions. An in-house software package MagiC is developed to obtain the effective potentials for arbitrary molecular systems. In this work we compute effective potentials to model DNA-protein interactions (bacterial LiaR regulator bound to a 26 base pairs DNA fragment) at physiological salt concentration at a coarse-grained (CG) level. Normally the IMC CG pair-potentials are used directly as look-up tables but here we have fitted them to five Gaussians and a repulsive wall. Results show stable association between DNA and the model protein as well as similar position fluctuation profile.

  • 41.
    Lyubartsev, Alexander P.
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Rabinovich, Alexander L.
    Force Field Development for Lipid Membrane Simulations2016In: Biochimica et Biophysica Acta - Biomembranes, ISSN 0005-2736, E-ISSN 1879-2642, Vol. 1858, no 10, 2483-2497 p.Article in journal (Refereed)
    Abstract [en]

    With the rapid development of computer power and wide availability of modelling software computer simulations of realistic models of lipid membranes, including their interactions with various molecular species, polypeptides and membrane proteins have become feasible for many research groups. The crucial issue of the reliability of such simulations is the quality of the force field, and many efforts, especially in the latest several years, have been devoted to parametrization and optimization of the force fields for biomembrane modelling. In this review, we give account of the recent development in this area, covering different classes of force fields, principles of the force field parametrization, comparison of the force fields, and their experimental validation. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Rog.

  • 42.
    Lyubartsev, Alexander P.
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Rabinovich, Alexander L.
    Recent development in computer simulations of lipid bilayers2011In: Soft Matter, ISSN 1744-683X, E-ISSN 1744-6848, Vol. 7, no 1, 25-39 p.Article, review/survey (Refereed)
    Abstract [en]

    Rapid development of computer power during the last decade has made molecular simulations of lipid bilayers feasible for many research groups, which, together with the growing general interest in investigations of these very important biological systems has lead to tremendous increase of the number of research on the computational modeling of lipid bilayers. In this review, we give account of the recent progress in computer simulations of lipid bilayers covering mainly the period of the last 5 years, and covering several selected subjects: development of the force fields for lipid bilayer simulations, studies of the role of lipid unsaturation, the effect of cholesterol and other inclusions on properties of the bilayer, and use of coarse-grained models.

  • 43.
    Lyubartsev, Alexander
    et al.
    Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry.
    Tu, Yaoquan
    Örebro university.
    Laaksonen, Aatto
    Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry.
    Hierarchical Multiscale Modelling Scheme from First Principles to Mesoscale2009In: Journal of computational and theoretical nanoscience, ISSN 1546-1963 (eISSN), Vol. 6, no 5, 951-959 p.Article in journal (Refereed)
    Abstract [en]

    We present a straight-forward implementation of a practical hierarchical multiscale modelling scheme which enables us to start from first-principles atomistic computer simulation and successively coarse-grain the model by leaving out uninteresting degrees of freedom. Using the Car-Parrinello method or our recently developed highly efficient tight-binding-like approximate density-functional quantum mechanical method, we first perform ab initio simulations. From these first-principles simulations we obtain a set of atomistic pair-wise effective interaction potentials to be used as a force field with no empirical data for subsequent classical all-atom simulations while scaling up the system size 2-3 orders of magnitude. The atomistic simulations similarly provide a new set of effective potentials but at a chosen coarse-grain level suitable for large-scale mesoscopic or soft-matter simulations beyond the atomic resolution. Several examples are shown of how this scheme is done based on effective interaction potentials to tie together the various scales of modelling.

  • 44.
    Mirzoev, Alexander
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Lyubartsev, Alexander
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Systematic implicit solvent coarse graining of DMPC lipidsArticle in journal (Refereed)
    Abstract [en]

    A 10-site coarse-grained implicit solvent model of DMPC phospholipid is developed with effective solvent-mediated potentials derived using the inverse Monte Carlo method. The potentials providing for the coarse-grained model the same site-site RDFs, bond and angle distributions as those computed in atomistic simulations were computed for four different lipid-water molar ratios.It was shown that there is a significant concentration dependence for both effective potentials and properties of lipid bilayers simulated using these potentials. Thus, effective potentials computed at low lipid concentration favour to more condensed and ordered structure of the bilayer with lower average area per lipid, while potentials obtained at higher lipid concentrations provide more fluid-like structure. Introduction of bending angle interaction into coarse-grained model makes effective potentials somewhat less concentration-dependent. The best agreement with the reference data and experiment was achieved using the set of potentials derived from atomistic simulations at 1:30 lipid:water molar ratio providing full hydration of DMPC lipids in bilayer. Despite theoretical limitations of the structure-based approach expressed in state point dependence of the effective potentials, all the resulting potentials provide a stable bilayer structure with correct partitioning of different lipid groups across the bilayer as well as acceptable values of the average lipid area and compressibility. Another important property demonstrated by the model is liquid/gel phase transition observed at lowering the temperature. In addition to bilayer simulations, the model has proven its robustness in modeling of self-aggregation of lipids from randomly dispersed solution to ordered bilayer structures, bicells and vesicles.

  • 45.
    Mirzoev, Alexander
    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.
    Effective solvent mediated potentials of Na+ and Cl ions in aqueous solution: temperature dependence2011In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, no 13, 5722-5727 p.Article in journal (Refereed)
    Abstract [en]

    The effective solvent-mediated potentials for Na+ and Cl ions in aqueous solution were calculated in a wide range of temperatures from 0 to 100 °C. The potentials have been determined using the inverse Monte Carlo approach, from the ion–ion radial distribution functions computed in 50 ns molecular dynamics simulations of ions and explicit water molecules. We further separated the effective potentials into a short-range part and an electrostatic long-range part represented by a coulombic potential with some dielectric permittivity. We adjusted the value of the dielectric permittivity to provide the fastest possible decay of the short-range potentials at larger distances. The obtained temperature dependence of the dielectric permittivity follows well the experimental data. We show also that the largest part of the temperature dependence of the effective potentials can be attributed to the temperature-dependent dielectric permittivity.

  • 46.
    Mirzoev, Alexander
    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.
    MagiC: Software Package for Multiscale Modeling2013In: Journal of Chemical Theory and Computation, ISSN 1549-9618, E-ISSN 1549-9626, Vol. 9, no 3, 1512-1520 p.Article in journal (Refereed)
    Abstract [en]

    We present software package MagiC, which is designed to perform systematic structure-based coarse graining of molecular models. The effective pairwise potentials between coarse-grained sites of low-resolution molecular models are constructed to reproduce structural distribution functions obtained from the modeling of the system in a high resolution (atomistic) description. The software supports coarse-grained tabulated intramolecular bond and angle interactions, as well as tabulated nonbonded interactions between different site types in the coarse-grained system, with the treatment of long-range electrostatic forces by the Ewald summation. Two methods of effective potential refinement are implemented: iterative Boltzmann inversion and inverse Monte Carlo, the latter accounting for cross-correlations between pair interactions. MagiC uses its own Metropolis Monte Carlo sampling engine, allowing parallel simulation of many copies of the system with subsequent averaging of the properties, which provides fast convergence of the method with nearly linear scaling at parallel execution.

  • 47.
    Mirzoev, Alexander
    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.
    Systematic Implicit Solvent Coarse Graining of Dimyristoylphosphatidylcholine Lipids2014In: Journal of Computational Chemistry, ISSN 0192-8651, E-ISSN 1096-987X, Vol. 35, no 16, 1208-1218 p.Article in journal (Refereed)
    Abstract [en]

    We have used systematic structure-based coarse graining to derive effective site-site potentials for a 10-site coarse-grained dimyristoylphosphatidylcholine (DMPC) lipid model and investigated their state point dependence. The potentials provide for the coarse-grained model the same site-site radial distribution functions, bond and angle distributions as those computed in atomistic simulations carried out at four different lipid-water molar ratios. It was shown that there is a non-negligible dependence of the effective potentials on the concentration at which they were generated, which is also manifested in the properties of the lipid bilayers simulated using these potentials. Thus, effective potentials computed at low lipid concentration favor to more condensed and ordered structure of the bilayer with lower average area per lipid, while potentials obtained at higher lipid concentrations provide more fluid-like structure. The best agreement with the reference data and experiment was achieved using the set of potentials derived from atomistic simulations at 1:30 lipid:water molar ratio providing fully saturated hydration of DMPC lipids. Despite theoretical limitations of pairwise coarse-grained potentials expressed in their state point dependence, all the resulting potentials provide a stable bilayer structure with correct partitioning of different lipid groups across the bilayer as well as acceptable values of the average lipid area, compressibility and orientational ordering. In addition to bilayer simulations, the model has proven its robustness in modeling of self-aggregation of lipids from randomly dispersed solution to ordered bilayer structures, bicelles, and vesicles.

  • 48.
    Mojumdar, Enamul
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Lyubartsev, Alexander
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    Molecular Dynamics Simulations of Local Anesthetic Articaine in a Lipid Bilayer2010In: Biophysical Chemistry, ISSN 0301-4622, E-ISSN 1873-4200, Vol. 153, no 1, 27-35 p.Article in journal (Refereed)
    Abstract [en]

    In order to investigate structural and dynamical propertiesof local anesthetic articaine in a model lipid bilayer, a series ofmolecular dynamics simulations have been performed. Simulations werecarried out for neutral and charged (protonated) forms of articaine insertedin fully hydrated dimyristoylphosphatidylcholine (DMPC) lipid bilayer. For comparison purpose, a fully hydrated DMPC bilayer withoutarticaine was also simulated. The length of each simulation was 200 ns. Various properties of the lipid bilayer systems in the presence of both charged and uncharged forms of articaine taken at two different concentrations have been examined: membrane area per lipid, mass density distributions, order parameters, radial distribution functions, head group tilt, diffusion coefficients, electrostatic potential, etc, and compared with results of previous simulations of DMPC bilayer in presence of lidocaine.It was shown that addition of both charged and neutral forms of articainecauses increase of the dipole electrostatic potential in the membraneinterior.

  • 49.
    Nikitin, Alexei
    et al.
    Institute of molecular biology, Moscow.
    Lyubartsev, Alexander
    Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry.
    New six-site acetonitrile model for simulations of liquid acetonitrile and its aqueous mixtures2007In: Journal of Computational Chemistry, ISSN 0192-8651, E-ISSN 1096-987X, Vol. 28, no 12, 2020-2026 p.Article in journal (Refereed)
    Abstract [en]

    A new six site flexible acetonitrile molecular model is developed. The AMBER force field was used for description of intramolecular parameters, the atomic charges were calculated from a high level ab initio theory and finally the Lennard-Jones parameters were tuned to fit the experimental density and evaporation heat. The obtained in this way model reproduces correctly densities of water-acetonitrile mixtures as well as provides qualitative description of the dielectric permittivity and self-diffusion coefficients.

  • 50. Nikitin, Alexei M.
    et al.
    Milchevskiy, Yury V.
    Lyubartsev, Alexander P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
    A new AMBER-compatible force field parameter set for alkanes2014In: Journal of Molecular Modeling, ISSN 1610-2940, E-ISSN 0948-5023, Vol. 20, no 3, 2143- p.Article in journal (Refereed)
    Abstract [en]

    We present a new force field parameter set for simulating alkanes. Its functional form and parameters are chosen to make it directly compatible with the AMBER94/99/12 family of force fields implemented in the available software. The proposed parameterization enables universal description of both the conformational and thermodynamic properties of linear, branched, and cyclic alkanes. Such unification is achieved by using two essential principles: (1) reduction of the Lennard-Jones radius for all sp3 carbons to 1.75 angstrom; (2) separate optimization of Lennard-Jones well depths for carbons with different degree of substitution. The new parameter set may prove to be optimal for description of alkyl residues in a broad range of biomolecules, from amino acids to lipids with their extended linear tails.

12 1 - 50 of 69
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