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  • 1. Ai, Yue-Jie
    et al.
    Liao, Rong-Zhen
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Chen, Shi-Lu
    Hua, Wei-Jie
    Fang, Wei-Hai
    Luo, Yi
    Repair of DNA Dewar Photoproduct to (6-4) Photoproduct in (6-4) Photolyase2011Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 115, nr 37, s. 10976-10982Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Dewar photoproduct (Dewar PP) is the valence isomer of (6-4) photoproduct ((6-4)PP) in photodamaged DNA. Compared to the extensive studied CPD photoproducts, the underlying repair mechanisms for the (6-4)PP, and especially for the Dewar PP, are not well-established to date. In this paper, the repair mechanism of DNA Dewar photoproduct T(dew)C in (6-4) photolyase was elucidated using hybrid density functional theory. Our results showed that, during the repair process, the T(dew)C has to isomerize to T(6-4)C photolesion first via direct C6'-N3' bond cleavage facilitated by electron injection. This isomerization mechanism is energetically much more efficient than other possible rearrangement pathways. The calculations provide a theoretical interpretation to recent experimental observations.

  • 2. Ai, Yue-Jie
    et al.
    Liao, Rong-zhen
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Chen, Shu-feng
    Luo, Yi
    Fang, Wei-Hai
    Theoretical Studies on Photoisomerizations of (6-4) and Dewar Photolesions in DNA2010Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 114, nr 44, s. 14096-14102Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The (6-4) photoproduct ((6-4) PP) is one of the main lesions in UV-induced DNA damage. The (6-4) PP and its valence isomer Dewar photoproduct (Dewar PP) can have a great threat of mutation and cancer but gained much less attention to date. In this study, with density functional theory (DFT) and the complete active space self-consistent field (CASSCF) methods, the photoisomerization processes between the (6-4) PP and the Dewar PP in the gas phase, the aqueous solution, and the photolyase have been carefully examined. Noticeably, the solvent effect is treated with the CASPT2//CASSCF/Amber (QM/MM) method. Our calculations show that the conical intersection (Cl) points play a crucial role in the photoisomerization reaction between the (6-4) PP and the Dewar PP in the gas and the aqueous solution. The ultrafast internal conversion between the S-2 ((1)pi pi*) and the So states via a distorted intersection point is found to be responsible for the formation of the Dewar PP lesion at 313 nm, as observed experimentally. For the reversed isomeric process, two channels involving the "dark" excited states have been identified. In addition to the above passages, in the photolyase, a new electron-injection isomerization process as an efficient way for the photorepair of the Dewar PP is revealed.

  • 3. Andersson, Ove
    et al.
    Häussermann, Ulrich
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    A Second Glass Transition in Pressure Collapsed Type II Clathrate Hydrates2018Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 122, nr 15, s. 4376-4384Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Type II clathrate hydrates (CHs) M-17 H2O, with M = tetrahydrofuran (THF) or 1,3-dioxolane, are known to collapse, or amorphize, on pressurization to similar to 1.3 GPa in the temperature range 77-140 K. On heating at 1 GPa, these pressure-amorphized CH states show a weak, stretched sigmoid-shaped, heat-capacity increase because of a glass transition. Here we use thermal conductivity and heat capacity measurements to show that also type II CH with M = cyclobutanone (CB) collapses on isothermal pressurization and undergoes a similar, weak, glass transition upon heating at 1 GPa. Furthermore, we reveal for both THF CH and CB CH a second, much more pronounced, glass transition at temperatures above the thermally weak glass transition on heating in the 0.2-0.7 GPa range. This result suggests the general occurrence of two glass transitions in water-rich (94 mol %) pressure-collapsed CHs. Because of a large increase in dielectric permittivity concurrently as the weak heat capacity increase, the first glass transition must be due to kinetic unfreezing of water molecules. The thermal features of the second glass transition, measured on isobaric temperature cycling, are typical of a glass liquid glass transition, which suggests that pressure-amorphized CHs transform reversibly to liquids.

  • 4.
    Angles d'Ortoli, Thibault
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Sjöberg, Nils A.
    Vasiljeva, Polina
    Lindman, Jonas
    Widmalm, Göran
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Bergenstråhle-Wohlert, Malin
    Wohlert, Jakob
    Temperature Dependence of Hydroxymethyl Group Rotamer Populations in Cellooligomers2015Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 119, nr 30, s. 9559-9570Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Empirical force fields for computer simulations of carbohydrates are often implicitly assumed to be valid also at temperatures different from room temperature for which they were optimited: Herein, the temperature dependence of the hydroxymethyl group rotamer populations in short oligogaccharides is invegtigated using Molecular dynamics simulations and NMR spectroscopy. Two oligosaccharides, methyl beta-cellobioside and beta-cellotetraose were simulated using three different carbohydrate force fields (CHARMM C35, GLYCAM06, and GROMOS 56A(carbo)) in combination with different water models (SPC, SPC/E, and TIP3P) using replica exchange molecular dynamics simulations. For comparison, hydroxymethyl group rotamer populations were investigated for methyl beta-cellobioside and cellopentaose based- on measured NMR (3)J(H5,H6) coupling constants, in the latter case by using a chemical shift selective NMR-filter. Molecular dynamics simulations in combination with NMR spectroscopy show that the temperature dependence of the hydroxymethyl rotamer population in these short cellooligomers, in the range 263-344 K, generally becomes exaggerated in simulations when compared to experimental data, but also that it is dependent on simulation conditions, and most notably properties of the water model.

  • 5.
    Bader, Reto
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum.
    Utilizing the Charge Field Effect on Amide N-15 Chemical Shifts for Protein Structure Validation2009Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 113, nr 1, s. 347-358Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Of all the nuclei in proteins, the nuclear magnetic resonance (NMR) chemical shifts of nitrogen are the theoretically least well understood. In this study, quantum chemical methods are used in combination with polarizable-continuum models in order to show that consideration of the effective electric field, including charge screening due to solvation, improves considerably the consistencies of statistical relationships between experimental and computed amide N-15 shifts between various sets of charged and uncharged oligopeptides and small organic molecules. A single conversion scheme between shielding parameters from first principles using density functional theory (DFT) and experimental shifts is derived that holds for all classes of compounds examined here. This relationship is then used to test the accuracy of such N-15 chemical shift predictions in the cyclic decapeptide antibiotic gramicidin S (GS). GS has previously been studied in great detail, both by NMR and X-ray crystallography. It adopts a well-defined backbone conformation, and hence, only a few discrete side chain conformational states need to be considered. Moreover, a charge-relay effect of the two cationic ornithine side chains to the protein backbone has been described earlier by NMR spectroscopy. Here, DFF-derived backbone amide nitrogen chemical shifts were calculated for multiple conformations of GS. Overall, the structural dynamics of GS is revisited in view of chemical shift behavior along with energetic considerations. Together, the study demonstrates proof of concept that N-15 chemical shift information is particularly useful in the analysis and validation of protein conformational states in a charged environment.

  • 6.
    Bassan, Arianna
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum.
    Blomberg, Margareta R. A.
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum.
    Borowski, Tomasz
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum.
    Siegbahn, Per E. M.
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum.
    Oxygen Activation by Rieske Non-Heme Iron Oxygenases, a Theoretical Insight2004Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 108, nr 34, s. 13031-13041Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The first steps of dioxygen activation in naphthalene 1,2-dioxygenase have been investigated by means of hybrid density functional theory. Reduction of molecular oxygen by this Rieske dioxygenase occurs in the catalytic domain accommodating a mononuclear non-heme iron(II) complex, and it requires two external electrons ultimately delivered by a Rieske [2Fe−2S] cluster hosted in the neighboring domain. Theoretical tools have been applied to gain insight into the O2-binding step and into the first one-electron-transfer process involving the mononuclear and the Rieske centers, and yielding an iron(II)−superoxo intermediate. The reaction, which is mimicked with a model including both metal sites, is found to be a reversible equilibrium. Although the entropic loss associated with the binding of O2 to iron(II) is not canceled by the corresponding enthalpic binding energy, it is, however, balanced by the exothermicity of the electron transfer process from the Rieske cluster to the dioxygen-bound iron(II) complex. The rationalization for the calculated energetics is related to the values of the ionization potential (IP) of the Rieske cluster and the electron affinity (EA) of the mononuclear iron complex: the latter is computed to be higher than the former, when dioxygen is bound to the metal. The possibility that a second external electron is delivered to the mononuclear site before dioxygenation of the substrate has also been examined. It is shown that, if the second electron is available in the Rieske domain, the electron transfer process is energetically favored. The results acquired with the large model comprising the two metal centers are compared to the corresponding information collected from the study of smaller models, where either the mononuclear iron complex or the Rieske cluster is included.

  • 7. Battistel, Marcos D.
    et al.
    Pendrill, Robert
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Widmalm, Göran
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Freedberg, Daron I.
    Direct Evidence for Hydrogen Bonding in Glycans: A Combined NMR and Molecular Dynamics Study2013Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 117, nr 17, s. 4860-4869Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We introduce the abundant hydroxyl groups of glycans as NMR handle's and structural probes to expand the repertoire of tools for structure function studies on glycans in solution. To this end, we present the facile detection and assignment of hydroxyl groups in a Wide range of sample concentrations (0.5-1700 mM) and temperatures, ranging from -5 to 25 degrees C.,We then exploit this information to directly detect hydrogen bonds, well-known for their importance in molecular structural determination through NMR. Via HSQC-TOCSY, we were able to determine the directionality; of these hydrogen bonds in sucrose Furthermore, by means Of molecular dynamics simulations in conjunction with NMR, we establish that one Out of the three detected hydrogen bonds arises from intermolecular interactions. This finding may shed light on glycan glycan interactions and glycan recognition by proteins.

  • 8. Bednarska, Joanna
    et al.
    Zalesny, Robert
    Murugan, N. Arul
    Bartkowiak, Wojciech
    Agren, Hans
    Odelius, Michael
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum.
    Elucidating the Mechanism of Zn2+ Sensing by a Bipyridine Probe Based on Two-Photon Absorption2016Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 120, nr 34, s. 9067-9075Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In this work, we examine, by means of computational methods, the mechanism of Zn2+ sensing by a bipyridine-centered, D-pi-A-pi-D-type-ratiometric molecular probe. According to recently published experimental data [Divya, K. P.; Sreejith, S.; Ashokkumar, P.; Yuzhan, K.; Peng, Q; Maji, S. K.; Tong, Y.; Yu, H.; Zhao, Y.; Ramamurthy, P.; Ajayaghosh, A. A ratiometric fluorescent molecular -probe with enhanced two-photon response upon Zn2+ binding for in vitro and in vivo: bioimaging.= Chem. Sci. 2014, S, 3469-3474], after coordination to zinc ions the -probe exhibits a large enhancement of the two -photon absorption cross section. The goal of our investigation was to elucidate the mechanism behind this phenomenon. For this purpose, linear and nonlinear optical properties of -the unbound (cation-free) and bound probe were calculated, including the influence of solute Solvent interactions, implicitly using a polarizable continuum model and exp-licitely employing the QM/MM approach. Because the results of the calculations indicate that many conformers of the probe are energetically accessible at room temperature in solution and hence contribute to the Signal, structurepteperty relationships were also taken into account. Results of our simulations-demonstrate that the one-photon absorption bands for both the unbound -and bound forms correspond to the bright pi -> pi* transition to the first excited state; which, on the other hand,. exhibits negligible two-photon activity. On the basis of the results of the quadratic respOnse calculations, we put forward-notion that it is the second excited state that gives the strong signal in the experimental nonlinear spectrum. To explain the differenCes in the two-photon absorption activity for the two lowest-lying excited states and nonlinear response enhancement upon binding, we employed the generalized few -state model including the ground, first, and- second excited states. The analysis of the optical channel suggests that the large two-photon response is due to the coordination -induced increase of the, transition- moment from the first to the second excited state.

  • 9. Blum, M.
    et al.
    Odelius, Michael
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum.
    Weinhardt, L.
    Pookpanratana, S.
    Baer, M.
    Zhang, Y.
    Fuchs, O.
    Yang, W.
    Umbach, E.
    Heske, C.
    Ultrafast Proton Dynamics in Aqueous Amino Acid Solutions Studied by Resonant Inelastic Soft X-ray Scattering2012Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 116, nr 46, s. 13757-13764Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Resonant inelastic soft X-ray scattering (RIXS) has been used to study the electronic structure of glycine and lysine in aqueous solution. Upon variation of the pH value of the solution from acidic to basic, major changes of the nitrogen K edge RIXS data are observed for both amino acids, which are associated with the protonation and deprotonation of the amino groups. The experimental results are compared with simulations based on density functional theory, yielding a detailed understanding of the spectral changes, as well as insights into the ultrafast proton dynamics in the intermediate core-excited/ionized state of the RIXS process.

  • 10. Botan, Alexandru
    et al.
    Favela-Rosales, Fernando
    Fuchs, Patrick F. J.
    Javanainen, Matti
    Kanduc, Matej
    Kulig, Waldemar
    Lamber, Antti
    Loison, Claire
    Lyubartsev, Alexander
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Miettinen, Markus S.
    Monticelli, Luca
    Maatta, Jukka
    Ollila, O. H. Samuli
    Retegan, Marius
    Rog, Tomasz
    Santuz, Hubert
    Tynkkynen, Joona
    Toward Atomistic Resolution Structure of Phosphatidylcholine Headgroup and Glycerol Backbone at Different Ambient Conditions2015Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 119, nr 49, s. 15075-15088Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Phospholipids are essential building blocks of biological membranes. Despite a vast amount of very accurate experimental data, the atomistic resolution structures sampled by the glycerol backbone and choline headgroup in phoshatidylcholine bilayers are not known. Atomistic resolution molecular dynamics simulations have the potential to resolve the structures, and to give an arrestingly intuitive interpretation of the experimental data, but only if the simulations reproduce the data within experimental accuracy. In the present work, we simulated phosphatidylcholine (PC) lipid bilayers with 13 different atomistic models, and compared simulations with NMR. experiments in terms of the highly structurally sensitive C-H bond vector order parameters. Focusing on the glycerol backbone and choline headgroups, we showed that the order parameter comparison can be used to judge the atomistic resolution structural accuracy of the models. Accurate models, in turn, allow molecular dynamics simulations to be used as an interpretation tool that translates these NMR data into a dynamic three-dimensional representation of biomolecules in biologically relevant conditions. In addition to lipid bilayers in fully hydrated conditions, we reviewed previous experimental data for dehydrated bilayers and cholesterol-containing bilayers, and interpreted them with simulations. Although none of the existing models reached experimental accuracy, by critically comparing them we were able to distill relevant chemical information: (1) increase of choline order parameters indicates the P-N vector tilting more parallel to the membrane, and (2) cholesterol induces only minor changes to the PC (glycerol backbone) structure. This work has been done as a fully open collaboration, using nmrlipids.blogspot.fi as a communication platform; all the scientific contributions were made publicly on this blog. During the open research process, the repository holding our simulation trajectories and files (https://zenodo.org/collection/user-nmrlipids) has become the most extensive publicly available collection of molecular dynamics simulation trajectories of lipid bilayers.

  • 11.
    Chen, Shi-Lu
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum.
    Blomberg, Margareta R. A.
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum.
    Siegbahn, Per E. M.
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum.
    How Is a Co-Methyl Intermediate Formed in the Reaction of Cobalamin-Dependent Methionine Synthase?: Theoretical Evidence for a Two-Step Methyl Cation Transfer Mechanism2011Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 115, nr 14, s. 4066-4077Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A methyl-Co(cobalamin) species has been characterized to be a crucial intermediate in the last step of the de novo biosynthesis of methionine catalyzed by cobalamin-dependent methionine synthase (MetH). However, exactly how it is formed is still an open question. In the present article, the formation of the methyl-Co(cobalamin) species in MetH has been investigated with B3LYP* hybrid DFT including van der Waals (vdW) interactions (i.e., dispersion) and using a chemical model built on X-ray crystal structures. The methyl cation and radical transfer mechanisms have been examined in various protonation states. The calculations reveal that the CH(3)-Co(III)(cobalamin) formation in MetH proceeds along a stepwise pathway, where the first step is a methyl cation transfer from the protonated methyltetrahydrofolate (CH(3)-THF) substrate to the Co(I)cobalamin. The second step is a binding of His759 to the other side (a-face) of Co. The former methyl transfer is computed to be the rate-limiting step with a barrier of 18 kcal/mol, which is reduced to 13 kcal/mol when dispersion is included. For the first step, the protonation at the methyl-bound nitrogen of CH(3)-THF is very important. The methyl transfer is otherwise unreachable with a very high barrier of similar to 38 kcal/mol. The deprotonation of the alpha-face His759-Asp757-Ser810 triad is found to be much less significant but slightly facilitates the CH(3)-Co(III)Cbl formation. There has been a long-standing discrepancy of 10-20 kcal/mol between theory and experiment in previous B3LYP computations of the Co C bond dissociation energy for the methyl-Co(cobalamin) species. The calculations indicate that the lack of dispersion (similar to 11 kcal/mol) is the main origin of this puzzling problem. With these effects, B3LYP* gives a bond strength of 32 kcal/mol compared to the experimental value of 37 +/- 3 kcal/mol. Overall, the present calculations give many examples of dispersion that makes non-negligible contributions to the energetics of enzyme reactions, especially for systems involving at least one large reacting fragment approaching or departing.

  • 12.
    Dahlberg, Martin
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för fysikalisk kemi, oorganisk kemi och strukturkemi.
    Polymorphic phase behavior of cardiolipin derivatives studied by coarse-grained molecular dynamics2007Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 111, nr 25, s. 7194-7200Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cardiolipin (CL) is a negatively charged four acyl chain lipid, associated with energy production in bacterial and mitochondrial membranes. Due to the shape of CL, negative curvatures of aggregates are favorable if the charges in the head group can be reduced. The phase polymorphism of CL, and of associated derivatives with 2, 3, 4, or 5 chains, has been determined previously and offers a model system in which micellar, lamellar, and inverse hexagonal phases can be observed. We present an extension to a previously established coarse-grained molecular dynamics model with the aim of reproducing the different CL phases with two adjustable parameters: the number of acyl chains and the effective head group charge. With molecular dynamics simulations of large lipid systems, we observed transitions between different phases on the nanosecond to microsecond time scale. Charge screening by high salt or low pH was successfully modeled by a reduction of phosphate charge, which led to the adoption of aggregates with more negative curvature. Although specific ion binding at the interface and other atomistic details are sacrificed in the coarse-grained model, we found that it captures general phase features over a large range of aggregate geometries.

  • 13. Egorov, Andrei V.
    et al.
    Lyubartsev, Alexander P.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK), Avdelningen för fysikalisk kemi.
    Laaksonen, Aatto
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK), Avdelningen för fysikalisk kemi.
    Molecular Dynamics Simulation Study of Glycerol-Water Liquid Mixtures2011Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 115, nr 49, s. 14572-14581Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 14. Ekimova, Maria
    et al.
    Kubin, Markus
    Ochmann, Miguel
    Ludwig, Jan
    Huse, Nils
    Wernet, Philippe
    Odelius, Michael
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum.
    Nibbering, Erik T. J.
    Soft X-ray Spectroscopy of the Amine Group: Hydrogen Bond Motifs in Alkylamine/Alkylammonium Acid-Base Pairs2018Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 122, nr 31, s. 7737-7746Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We use N K-edge absorption spectroscopy to explore the electronic structure of the amine group, one of the most prototypical chemical functionalities playing a key role in acid base chemistry, electron donor-acceptor interactions, and nucleophilic substitution reactions. In this study, we focus on aliphatic amines and make use of the nitrogen is core electron excitations to elucidate the roles of N-H sigma* and N-C sigma* contributions in the unoccupied orbitals. We have measured N K-edge absorption spectra of the ethylamine bases EtxNH3-x (x = 0...3; Et- = C2H5-) and the conjugate positively charged ethylammonium cation acids EtyNH4-y+ (y = 0...4; Et- = C2H5-) dissolved in the protic solvents ethanol and water. Upon consecutive exchange of N-H for ethyl-groups, we observe a spectral shift, a systematic decrease of the N K-edge pre-edge peak, and a major contribution in the post edge region for the ethylamine series. Instead, for the ethylammonium ions, the consecutive exchange of N-H for ethyl groups leads to an apparent reduction of pre-edge and post-edge intensities relative to the main-edge band, without significant frequency shifts. Building on findings from our previously reported study on aqueous ammonia and ammonium ions, we can rationalize these observations by comparing calculated N K-edge absorption spectra of free and hydrogen-bonded clusters. Hydrogen bonding interactions lead only to minor spectral effects in the ethylamine series, but have a large impact in the ethylammonium ion series. Visualization of the unoccupied molecular orbitals shows the consecutive change in molecular orbital character from N-H sigma* to N-C sigma* in these alkylamine/alkylammonium ion series. This can act as a benchmark for future studies on chemically more involved amine compounds.

  • 15. Engin, Ozge
    et al.
    Villa, Alessandra
    Sayar, Mehmet
    Hess, Berk
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Driving Forces for Adsorption of Amphiphilic Peptides to the Air-Water Interface2010Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 114, nr 34, s. 11093-11101Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We have studied the partitioning of amphiphilic peptides at the air-water interface. The free energy of adsorption from bulk to interface was calculated by determining the potential of mean force via atomistic molecular dynamics simulations. To this end a method is introduced to restrain or constrain the center of mass of a group of molecules in a periodic system. The model amphiphilic peptides are composed of alternating valine and asparagine residues. The decomposition of the free energy difference between the bulk and interface is studied for different peptide block lengths. Our analysis revealed that for short amphiphilic peptides the surface driving force dominantly stems from the dehydration of hydrophobic side chains. The only opposing force is associated with the loss of orientational freedom of the peptide at the interface. For the peptides studied, the free energy difference scales linearly with the size of the molecule, since the peptides mainly adopt extended conformations both in bulk and at the interface. The free energy difference depends strongly on the water model, which can be rationalized through the hydration thermodynamics of hydrophobic solutes. Finally, we measured the reduction of the surface tension associated with complete coverage of the interface with peptides.

  • 16.
    Engström, Olof
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Mobarak, Hani
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Ståhle, Jonas
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Widmalm, Göran
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Conformational Dynamics and Exchange Kinetics of N-Formyl and N-Acetyl Groups Substituting 3-Amino-3,6-dideoxy-alpha-D-galactopyranose, a Sugar Found in Bacterial O-Antigen Polysaccharides2017Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 121, nr 41, s. 9487-9497Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Three dimensional shape and conformation of. carbohydrates are important factors in molecular recognition events and the N-acetyl group of a monosaccharide residue can function as a conformational gatekeeper whereby it influences the overall shape of the oligosaccharide. NMR spectroscopy and quantum mechanics (QM) calculations are used herein to investigate both the conformational preferences and the dynamic behavior of N-acetyl and N-formyl substituents of 3-amino-3,6-dideoxy-alpha-D-galactopyranose, a sugar and substitution pattern found in bacterial O-antigen polysaccharides. QM calculations suggest that the amide oxygen can be involved in hydrogen bonding with the axial OH4 group primarily but also with the equatorial OH2 group. However, an NMR J coupling analysis indicates that the 01 torsion angle, adjacent to the sugar ring, prefers an ap conformation where conformations <180 degrees also are accessible, but does not allow for intramolecular hydrogen bonding. In the formyl-substituted compound (4)J(HH) coupling constants to the exo-cyclic group were detected and analyzed. A van't Hoff analysis revealed that the trans conformation at the amide bond is favored by Delta G degrees approximate to - 0.8 kcal.mol(-1) in the formyl-containing compound and with Delta G degrees approximate to -2.5 kcal.mol(-1) when the N-acetyl group is the substituent. In both cases the enthalpic term dominates to the free energy, irrespective of water or DMSO as solvent, with only a small contribution from the entropic term. The cis-trans isomerization of the theta(2) torsion angle, centered at the amide bond, was also investigated by employing H-1 NMR line shape analysis and C-13 NMR saturation transfer experiments. The extracted transition rate constants were utilized to calculate transition energy barriers that were found to be about 20 kcal.mol(-1) in both DMSO-d(6) and D2O. Enthalpy had a higher contribution to the energy barriers in DMSO-d(6) compared to in D2O, where entropy compensated for the loss of enthalpy.

  • 17.
    Eremina, Nadejda
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Barth, Andreas
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Use of Creatine Kinase To Induce Multistep Reactions in Infrared Spectroscopic Experiments2013Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 117, nr 48, s. 14967-14972Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    An extension of current approaches to trigger enzymatic reactions in reaction-induced infrared difference spectroscopy experiments is described. A common procedure is to add a compound that induces a reaction in the protein of interest. To be able to induce multistep reactions, we explored here the use of creatine kinase (CK) for the study of phosphate transfer mechanisms. The enzymatic reaction of CK could be followed using bands at 1614 and 979 cm(-1) for creatine phosphate consumption, at 944 cm(-1) for ADP consumption, and at 1243, 992, and 917 cm(-1) for ATP formation. The potential of CK to induce multistep reactions in infrared spectroscopic experiments was demonstrated using the sarcoplasmic reticulum Ca2+-ATPase (SERCA1a) as the protein of interest. ADP binding to the ATPase was triggered by photolytic release of ADP from P-3-1-(2-nitro)phenylethyl ADP (caged ADP). CK added in small amounts converted the released ADP to ATP on the time scale of minutes. This phosphorylated the ATPase and led to the formation of the first phosphoenzyme intermediate Ca(2)E1P. Thus a difference spectrum could be obtained that reflected the reaction from the ADP ATPase complex to the first phosphoenzyme intermediate. Comparison with a phosphorylation spectrum obtained when the initial state was the ATP ATPase complex revealed the contribution of ATP's gamma-phosphate to the conformational change of the ATPase upon nucleotide binding: gamma-phosphate binding modifies the structure of a beta-sheet, likely in the phosphorylation domain, and shifts its spectral position from similar to 1640 to similar to 1630 cm(-1). Upon phosphorylation of the ATPase, the beta-sheet relaxes back to a structure that is intermediate between that adopted in the ADP bound state and that in the ATP bound state.

  • 18. Eriksson, Susanna K.
    et al.
    Josefsson, Ida
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum.
    Ottosson, Niklas
    Öhrwall, Gunnar
    Björneholm, Olle
    Siegbahn, Hans
    Hagfeldt, Anders
    Odelius, Michael
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum.
    Rensmo, Hakan
    Solvent Dependence of the Electronic Structure of I- and I-3(-)2014Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 118, nr 11, s. 3164-3174Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We present synchrotron-based I4d photoelectron spectroscopy experiments of solutions from LiI and LiI3 in water, ethanol, and acetonitrile. The experimentally determined solvent-induced binding energy shifts (SIBES) for the monatomic I- anion are compared to predictions from simple Born theory, PCM calculations, as well as multiconfigurational quantum chemical spectral calculations from geometries obtained through molecular dynamics of solvated clusters. We show that the SIBES for I- explicitly depend on the details of the hydrogen bonding configurations of the solvent to the I- and that static continuum models such as the Born model cannot capture the trends in the SIBES observed both in experiments and in higher-level calculations. To extend the discussion to more complex polyatomic anions, we also performed experiments on I-3(-) and I-/I-3(-) mixtures in different solvents and the results are analyzed in the perspective of SIBES. The experimental SIBES values indicate that the solvation effects even for such similar anions as I- and I-3(-) can be rather different in nature.

  • 19.
    Ermilova, Inna
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Lyubartsev, Alexander P.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Extension of the Slipids Force Field to Polyunsaturated Lipids2016Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 120, nr 50, s. 12826-12842Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 20. Ganguly, Pritam
    et al.
    Schravendijk, Pim
    Hess, Berk
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    van der Vegt, Nico F. A.
    Ion Pairing in Aqueous Electrolyte Solutions with Biologically Relevant Anions2011Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 115, nr 13, s. 3734-3739Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We performed molecular simulations to study ion pairing in aqueous solutions. Our results indicate that ion specific interactions of Li(+), Na(+), and K(+) with the dimethyl phosphate anion are solvent-mediated. The same mechanism applies to carboxylate ions, as has been illustrated in earlier simulations of aqueous alkali acetate solutions. Contact ion pairs play only a minor role or no role at all in determining the solution structure and ion specific thermodynamics of these systems. On the basis of the Kirkwood Buff theory of solution we furthermore show that the well-known reversal of the Hofmeister series of salt activity coefficients, comparing chloride or bromide with dimethyl phosphate or acetate, is caused by changing from a contact pairing mechanism in the former system to a solvent-mediated interaction mechanism in the latter system.

  • 21.
    Georgiev, Valentin
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum.
    Noack, Holger
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum.
    Blomberg, Margareta R.A.
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum.
    Siegbahn, Per E.M.
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum.
    A DFT Study on the Catalytic Reactivity of a Functional Model Complex for  Intradiol-Cleaving Dioxygenases2010Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 114, nr 17, s. 5878-5885Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The enzymatic ring cleavage of catechol derivatives is catalyzed by two groups of dioxygenases: extradiol- and intradiol-cleaving dioxygenases. Although having different oxidation state of their nonheme iron sites and different ligand coordinations, both groups of enzymes involve a common peroxy intermediate in their catalytic cycles. The factors that lead to either extradiol cleavage resulting in 2-hydroxymuconaldehyde or intradiol cleavage resulting in muconic acid are not fully understood. Well-characterized model compounds that mimic the functionality of these enzymes offer a basis for direct comparison to theoretical results. In this study the mechanism of a biomimetic iron complex is investigated with density functional theory (DFT). This complex catalyzes the ring opening of catecholate with exclusive formation of the intradiol cleaved product. Several spin states are possible for the transition metal system, with the quartet state found to be of main importance during the reaction course. The mechanism investigated provides an explanation for the observed selectivity of the complex. First, a bridging peroxide is formed, which decomposes to an alkoxy radical by O−O homolysis. In contrast to the subsequent barrier-free intradiol C−C bond cleavage, the extradiol pathway proceeds via the formation of an epoxide, which requires an additional activation barrier.

  • 22.
    Grote, Fredrik
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Ermilova, Inna
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Lyubartsev, Alexander P.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Molecular Dynamics Simulations of Furfural and 5-Hydroxymethylfurfural at Ambient and Hydrothermal Conditions2018Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 122, nr 35, s. 8416-8428Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 23. Hatcher, Elizabeth
    et al.
    Säwén, Elin
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Widmalm, Göran
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    MacKerell, Jr., Alexander D.
    Conformational properties of methyl β-maltoside and methyl α- and β-cellobioside disaccharides2011Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 115, nr 3, s. 597-608Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    An investigation of the conformational properties of methyl β-maltoside, methyl α-cellobioside, and methyl β-cellobioside disaccharides using NMR spectroscopy and molecular dynamics (MD) techniques, is presented. Emphasis is placed on validation of a recently presented force field for hexopyranose disaccharides followed by elucidation of the conformational properties of two different types of glycosidic linkages, α-(1 → 4) and β-(1 → 4). Both gas-phase and aqueous-phase simulations are performed to gain insight into the effect of solvent on the conformational properties. A number of transglycosidic J-coupling constants and proton−proton distances are calculated from the simulations and are used to identify the percent sampling of the three glycosidic conformations (syn, anti-, and anti-ψ) and, in turn, describe the flexibility around the glycosidic linkage. The results show the force field to be in overall good agreement with experiment, although some very small limitations are evident. Subsequently, a thorough hydrogen bonding analysis is performed to obtain insights into the conformational properties of the disaccharides. In methyl β-maltoside, competition between HO2′−O3 intramolecular hydrogen bonding and intermolecular hydrogen bonding of those groups with solvent leads to increased sampling of syn, anti-, and anti-ψ conformations and better agreement with NMR J-coupling constants. In methyl α- and β-cellobioside, O5′−HO6 and HO2′−O3 hydrogen bonding interactions are in competition with intermolecular hydrogen bonding involving the solvent molecules. This competition leads to retention of the O5′−HO3 hydrogen bond and increased sampling of the syn region of the /ψ map. Moreover, glycosidic torsions are correlated to the intramolecular hydrogen bonding occurring in the molecules. The present results verify that in the β-(1 → 4)-linkage intramolecular hydrogen bonding in the aqueous phase is due to the decreased ability of water to successfully compete for the O5′ and HO3 hydrogen bonding moieties, in contrast to that occurring between the O5′ and HO6 atoms in this α-(1 → 4)-linkage.

  • 24. He, Xibing
    et al.
    Hatcher, Elizabeth
    Eriksson, Lars
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Widmalm, Göran
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    MacKerell, Alexander D., Jr.
    Bifurcated Hydrogen Bonding and Asymmetric Fluctuations in a Carbohydrate Crystal Studied via X-ray Crystallography and Computational Analysis2013Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 117, nr 25, s. 7546-7553Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The structure of the O-methyl glycoside of the naturally occurring 6-O-[(R)-1-carboxyethyl]-alpha-D-galactopyranose, C10H18O8, has been determined by X-ray crystallography at 100 K, supplementing the previously determined structure obtained at 293 K (Acta Crystallogr. 1996, C52, 2285-2287). Molecular dynamics simulations of this glycoside were Performed in the crystal environment with different numbers of units cells included in the primary simulation system at both 100 and 293 K. The Calculated unit cell Parameters and the intramolecular geometries (bonds, angles, and dihedrals) agree well with experimental results. Atomic fluctuations, including B-factors and anisotropies, are in good agreement with respect to the relative values on an atom-by-atom basis. In addition, the fluctuations increase with increasing simulation system size, with the simulated values converging to values lower than those observed experimentally indicating that the simulation model is not accounting for all possible contributions to the experimentally observed B-factors, which may be related to either the simulation time scale or size. In the simulation's, the hydroxyl group of O7 is found to from bifurcated hydrogen bonds with O6 and O8 of an adjacent molecule, with the interactions dominated by the interaction HO7-O6 interaction. Quantum mechanical calculations support this observation.

  • 25.
    Heshmat, Mojgan
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Privalov, Timofei
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Water and a Borohydride/Hydronium Intermediate in the Borane-Catalyzed Hydrogenation of Carbonyl Compounds with H-2 in Wet Ether: A Computational Study2018Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 122, nr 38, s. 8952-8962Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We have computationally evaluated water as an active Lewis base (LB) and introduced the borohydride/hydronium intermediate in the mechanism of B(C6F5)(3)-catalyzed hydrogenation of carbonyl compounds with H-2 in wet/moist ether. Our calculations extend the known frustrated Lewis pair mechanism of this reaction toward the inclusion of water as the active participant in all steps. Although the definition of the zero-energy point interweaves in comparison of the scenarios with and without water, we will be able to show that (i) water (hydrogen bonded to its molecular environment) can, in principle, act as a reasonably viable LB in cooperation with the borane Lewis acid such as B(C6F5)(3) but relatively a strong borane-water complexation can be the hindering factor; (ii) the herein-proposed borohydride/hydronium intermediates with the hydronium cation having three OH center dot center dot center dot ether hydrogen bonds or a combination of the OH center dot center dot center dot ether/OH center dot center dot center dot ketone hydrogen bonds appear to be as valid as the previously considered borohydride/oxonium or borohydride/oxocarbenium intermediates; (iii) the proton-coupled hydride transfer from the borohydride/hydronium to a ketone (acetone) has a reasonably low barrier. Our findings could be useful for better mechanistic understanding and further development of the aforementioned reaction.

  • 26. Jo, Sunhwan
    et al.
    Myatt, Daniel
    Qi, Yifei
    Doutch, James
    Clifton, Luke A.
    Im, Wonpil
    Widmalm, Göran
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Multiple Conformational States Contribute to the 3D Structure of a Glucan Decasaccharide: A Combined SAXS and MD Simulation Study2018Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 122, nr 3, s. 1169-1175Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The inherent flexibility of carbohydrates is dependent on stereochemical arrangements, and characterization of their influence and importance will give insight into the three-dimensional structure and dynamics. In this study, a beta-(1 -> 4)/beta-(1 -> 3)-linked glucosyl decasaccharide is experimentally investigated by synchrotron small-angle X-ray scattering from which its radius of gyration (R-g) is obtained. Molecular dynamics (MD) simulations of the decasaccharide show four populated states at each glycosidic linkage, namely, syn- and anti-conformations. The calculated R-g values from the MD simulation reveal that in addition to syn-conformers the presence of anti-psi conformational states is required to reproduce experimental scattering data, unveiling inherent glycosidic linkage flexibility. The CHARMM36 force field for carbohydrates thus describes the conformational flexibility of the decasaccharide very well and captures the conceptual importance that anti-conformers are to be anticipated at glycosidic linkages of carbohydrates.

  • 27.
    Johansson, Anna CV
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Lindahl, Erik
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Titratable amino acid solvation in lipid membranes as a function of protonation state2009Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 113, nr 1, s. 245-253Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Knowledge about the insertion and stabilization of membrane proteins is a key step toward understanding their function and enabling membrane protein design. Transmembrane helices are normally quite hydrophobic so as to efficiently insert into membranes, but there are many exceptions with polar or titratable residues. An obvious example is the S4 helices of voltage-gated ion channels with up to 4 arginines, leading to vivid discussion about whether such helices can insert spontaneously, and if so, what their conformation, protonation state, and cost of insertion really are. To address this question, we have determined geometric and energetic solvation properties for different protonation states of the titrateable amino acids, including hydration, side chain orientation, free energy profiles, and effects on the membrane thickness. As expected, charged states are significantly more expensive to insert (8-16 kcal/mol) than neutral variants (1-3 kcal/mol). Although both sets of values exhibit quite high relative correlation with experimental in vivo hydrophobicity scales, the magnitudes of the in vivo hydrophobicity scales are much lower and strikingly appears as a compressed version of the calculated values. This agrees well with computational studies on longer lipids but results in an obvious paradox: the differences between in vivo insertion and simulations cannot be explained by methodological differences in force fields, possible limited hydrophobic thickness of the endoplasmic reticulum (ER) membrane, or parameters; even anionic lipid head groups (PG) only have limited effect on charged side chains, and virtually none for hydrophobic ones. This leads us to propose a model for in vivo insertion that could reconcile these differences and explain the correlation: if there are considerable hydrophobic barriers inside the translocon, the experimental reference state for the solvation free energy when comparing insertion/translocation in vivo would be quite close to the bilayer environment rather than water.

  • 28.
    Jämbeck, Joakim P. M.
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK), Avdelningen för fysikalisk kemi.
    Lyubartsev, Alexander P.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK), Avdelningen för fysikalisk kemi.
    Derivation and Systematic Validation of a Refined All-Atom Force Field for Phosphatidylcholine Lipids2012Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 116, nr 10, s. 3164-3179Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 29.
    Jämbeck, Joakim P. M.
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK), Avdelningen för fysikalisk kemi.
    Lyubartsev, Alexander P.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK), Avdelningen för fysikalisk kemi.
    Update to the General Amber Force Field for Small Solutes with an Emphasis on Free Energies of Hydration2014Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 118, nr 14, s. 3793-3804Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 30.
    Kapla, Jon
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Stevensson, Baltzar
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Dahlberg, Martin
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Maliniak, Arnold
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Molecular Dynamics Simulations of Membranes Composed of Glycolipids and Phospholipids2012Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 116, nr 1, s. 244-252Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Lipid membranes composed of 1,2-di-(9Z,12Z,15Z)-octade-catrienoyl-3-O-β-D-galactosyl-sn-glycerol or monogalactosyldiacylglycerol(MGDG) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) were studied by means of molecular dynamics (MD) computer simulations. Three lipid compositions were considered: 0%, 20%, and 45% MGDG (by mole) denoted as MG-0, MG-20, and MG-45, respectively. The article is focused on the calculation of NMR dipolar interactions, which were confronted with previously reported experimental couplings. Dynamical processes and orientational distributions relevant for the averaging of dipolar interactions were evaluated. Furthermore, several parameters important for characterization of the bilayer structure, molecular organization, and dynamics were investigated. In general, only a minor change in DMPC properties was observed upon the increased MGDG/DMPC ratio, whereas properties related to MGDG undergo a more pronounced change. This effect was ascribed to the fact that DMPC is a bilayer (Lα) forming lipid, whereas MGDG prefers a reverse hexagonal (HII) arrangement.

  • 31.
    Kapla, Jon
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Stevensson, Baltzar
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Maliniak, Arnold
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Coarse-Grained Molecular Dynamics Simulations of Membrane Trehalose Interactions2016Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 120, nr 36, s. 9621-9631Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    It is well established that trehalose (TRH) affects the physical properties of lipid bilayers and stabilizes biological membranes. We present molecular dynamics (MD) computer simulations to investigate the interactions between lipid membranes formed by 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and TRH. Both atomistic and coarse-grained (CG) interaction models were employed, and the coarse graining of DMPC leads to a reduction in the acyl chain length corresponding to a 1,2-dilauroyl-sn-glycero-3-phosphocholine lipid (DLPC). Several modifications of the Martini interaction model, used for CG simulations, were implemented, resulting in different potentials of mean force (PMFs) for DMPC bilayer TRH interactions. These PMFs were subsequently used in a simple two-site analytical model for the description of sugar binding at the membrane interface. In contrast to that in atomistic MD simulations, the binding in the CG model was not in agreement with the two-site model. Our interpretation is that the interaction balance, involving water, TRH, and lipids, in the CG systems needs further tuning of the force-field parameters. The area per lipid is only weakly affected by TRH concentration, whereas the compressibility modulus related to the fluctuations of the membrane increases with an increase in TRH content. In agreement with experimental findings, the bending modulus is not affected by the inclusion of TRH. The important aspects of lipid bilayer interactions with biomolecules are membrane curvature generation and sensing. In the present investigation, membrane curvature is generated by artificial buckling of the bilayer in one dimension. It turns out that TRH prefers the regions with the highest curvature, which enables the most favorable situation for lipid sugar interactions.

  • 32.
    Kapla, Jon
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Wohlert, Jakob
    Stevensson, Baltzar
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Engström, Olof
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Widmalm, Göran
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Maliniak, Arnold
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Molecular Dynamics Simulations of Membrane-Sugar Interactions2013Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 117, nr 22, s. 6667-6673Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    It is well documented that disaccharides in general and trehalose (TRH) in particular strongly affect physical properties and functionality of lipid bilayers. We investigate interactions between lipid membranes formed by 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and TRH by means of molecular dynamics (MD) computer simulations. Ten different TRH concentrations were studied in the range W-TRH = 0-0.20 (w/w). The potential of mean force (PMF) for DMPC bilayer TRH interactions was determined using two different force fields, and was subsequently used in a simple analytical model for description of sugar binding at the membrane interface. The MD results were in good agreement with the predictions of the model. The net affinities of TRH for the DMPC bilayer derived from the model and MD simulations were compared with experimental results. The area per lipid increases and the membrane becomes thinner with increased TRH concentration, which is interpreted as an intercalation effect of the TRH molecules into the polar part of the lipids, resulting in conformational changes in the chains. These results are consistent with recent experimental observations. The compressibility modulus related to the fluctuations of the membrane increases dramatically with increased TRH concentration, which indicates higher order and rigidity of the bilayer. This is also reflected in a decrease (by a factor of 15) of the lateral diffusion of the lipids. We interpret these observations as a formation of a glassy state at the interface of the membrane, which has been suggested in the literature as a hypothesis for the membrane sugar interactions.

  • 33.
    Karjalainen, Eeva-Liisa
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Barth, Andreas
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Vibrational Coupling between Helices Influences the Amide I Infrared Absorption of Proteins: Application to Bacteriorhodopsin and Rhodopsin2012Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 116, nr 15, s. 4448-4456Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The amide 1 spectrum of multimers of helical protein segments was simulated using transition dipole coupling (TDC) for long-range interactions between individual amide oscillators and DFT data from dipeptides (la Cour Jansen et al. J. Chem. Phys. 2006, 125, 44312) for nearest neighbor interactions. Vibrational coupling between amide groups on different helices shift the helix absorption to higher wavenumbers. This effect is small for helix dimers (1 cm(-1)) at 10 angstrom distance and only moderately affected by changes in the relative orientation between the helices. However, the effect becomes considerable when several helices are bundled in membrane proteins. Particular examples are the 7-helix membrane proteins bacteriorhodopsin (BR) and rhodopsin, where the upshift is 4.3 and 5.3 cm(-1) respectively, due to interhelical coupling within a BR monomer. A further upshift of 4.0 cm(-1) occurs when BR monomers associate to trimers. We propose that interhelical vibrational coupling explains the experimentally observed unusually high wavenumber of the amide I band of BR

  • 34.
    Karjalainen, Eeva-Liisa
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Ersmark, Tore
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Barth, Andreas
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Optimization of Model Parameters for Describing the Amide I Spectrum of a Large Set of Proteins2012Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 116, nr 16, s. 4831-4842Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A new simulation protocol for the prediction of the infrared absorption of the amide I vibration of proteins was developed. The method incorporates known effects on the intrinsic frequencies (backbone conformation, interpeptide and peptide-solvent hydrogen bonding) and couplings (nearest neighbor coupling, transition dipole coupling) of amide I oscillators in a parametrized manner. Model parameters for the simulation of amide I spectra were determined through fitting and optimization of simulated spectra to experimentally measured infrared spectra of 44 proteins that represent maximum structural variation in terms of different folds and secondary structure contents. Prediction of protein spectra using the optimized parameters resulted in good agreement with experimental spectra and in a considerable improvement compared to a description involving only transition dipole coupling.

  • 35.
    Karjalainen, Eeva-Liisa
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Ravi, Harish Kumar
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Barth, Andreas
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Simulation of the Amide I Absorption of Stacked β-Sheets2011Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 115, nr 4, s. 749-757Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aggregated β-sheet structures are associated with amyloid and prion diseases. Techniques capable of revealing detailed structural and dynamical information on β-sheet structure are thus of great biomedical and biophysical interest. In this work, the infrared (IR) amide I spectral characteristics of stacked β-sheets were modeled using the transition dipole coupling model. For a test set of β-sheet stacks, the simulated amide I spectrum was analyzed with respect to the following parameters; intersheet distance, relative rotation of the sheets with respect to each other and the effect of number of sheets stacked. The amide I maximum shifts about 5 cm(-1) to higher wavenumbers when the intersheet distance between two identical β-sheets decreases from 20 to 5 Å. Rotation around the normal of one of the sheets relative to the other results in maximum intersheet coupling near 0° and 180°. Upon of rotation from 0° to 90° at an intersheet distance of 9 Å, the amide I maximum shifts about 3 cm(-1). Tilting of one of the sheets by 30° from the normal results in a shift of the amide I maximum by less than 1 cm(-1). When stacking several β-sheets along the normal, the amide I maximum shifts to higher wavenumbers with increasing stack size. The amide I maximum shifts about 6 cm(-1) when stacking four sheets with an intersheet distance of 9 Å. The study provides an aid in the interpretation of the IR amide I region for experiments involving β-sheets and creates awareness of the many effects that determine the spectrum of β-sheet structures.

  • 36. Kotsyubynskyy, Dmytro
    et al.
    Zerbetto, Mirco
    Šoltésová, Mária
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK). Charles University Prague .
    Engström, Olof
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Pendrill, Robert
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Kowalewski, Josef
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Widmalm, Göran
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Polimeno, Antonin
    Stochastic Modeling of Flexible Biomolecules Applied to NMR Relaxation: 2. Interpretation of Complex Dynamics in Linear Oligosaccharides2012Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 116, nr 50, s. 14541-14555Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A computational stochastic approach is applied to the description of flexible molecules. By combining (i) molecular dynamics simulations, (ii) hydrodynamics approaches, and (iii) a multidimensional diffusive description for internal and global dynamics, it is possible to build an efficient integrated approach to the interpretation of relaxation processes in flexible systems. In particular, the model is applied to the interpretation of nuclear magnetic relaxation measurements of linear oligosaccharides, namely a mannose-containing trisaccharide and the pentasaccharide LNF-1. Experimental data are reproduced with sufficient accuracy without free model parameters.

  • 37.
    Kumar, Saroj
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Barth, Andreas
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Effects of ions on ligand binding to pyruvate kinase: Mapping the binding site by infrared spectroscopyInngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207Artikkel i tidsskrift (Fagfellevurdert)
  • 38.
    Kumar, Saroj
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Barth, Andreas
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Effects of Ions on Ligand Binding to Pyruvate Kinase: Mapping the Binding Site with Infrared Spectroscopy2011Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 115, nr 20, s. 6784-6789Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The effects of mono- and divalent ions (Li(+), K(+), Na(+), Cs(+), Mg(2+), Ca(2+); Mn(2+), Zn(2+)) on the binding of phosphoenolpyruvate (PEP) to rabbit muscle pyruvate kinase (PK) were studied by attenuated total reflection infrared spectroscopy in combination with a dialysis accessory. The experiments assessed the structural change of the protein as well as the binding mode of PEP. They indicated that a signal at 1638 cm(-1) assigned to a beta sheet was perturbed differently with Na(+) as compared to the other monovalent ions. Otherwise, we obtained similar conformational changes in the presence of different monovalent cations, and therefore, it seems unlikely that the ion effects on activity are due to an ion effect on the structure of the PEP:PK complex. With different divalent cations, a particularly large conformational change was observed with Mn(2+) and attributed to a more closed conformation of the complex The absorption of bound PEP was also detected. The antisymmetric stretching vibration of the carboxylate group of bound PEP indicates a more homogeneous binding mode for Mn(2+) compared to the other divalent ions. The symmetric stretching vibration depends on both monovalent and divalent ions, indicating that the dihedral angle O-C(1)-C(2)-O is affected by the ions in the catalytic site. Little change in the bond strengths of PEP is observed, indicating that the PEP:PK complex does not adopt a reactive conformation.

  • 39.
    Kumar, Saroj
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Barth, Andreas
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    The Allosteric Effect of Fructose Bisphosphate on Muscle Pyruvate Kinase Studied by Infrared Spectroscopy2011Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 115, nr 39, s. 11501-11505Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Pyruvate kinase exhibits allosteric properties. The allosteric effect of fructose 1,6-bisphosphate (FBP) on phosphoenolpyruvate (PEP) binding to rabbit muscle pyruvate kinase (PK) in the presence of various ions (mg(2+), mn(2+), Na(+)) was studied by attenuated total reflection infrared spectroscopy in combination with a dialysis accessory. The experiments indicated that FBP binding causes conformational changes of PK that are of the same order of magnitude as those of PEP binding. The conformational change of PEP binding to PK/Mg(2+)/K(+) in the presence of FBP was about twice as large as in its absence, which is tentatively ascribed to a higher occupancy the closed state. The affinity for PEP increased in the presence of Mg(2+) and K(+). No such effects were observed with the other ion combinations Mn(2+)/K(+) and Mg(2+)/Na(+) or in D(2)O (with Mg(2+)/K(+)), and therefore we did not detect an allosteric effect on PEP binding under these conditions.

  • 40.
    Kumar, Saroj
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Eremina, Nadejda
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Barth, Andreas
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Detection of Ligand Binding to Proteins through Observation of Hydration Water2012Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 116, nr 48, s. 13968-13974Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Drug development is impeded by the need to design for each drug target a test that detects the binding of drug candidate molecules to the target protein. Therefore, a general method to detect ligand binding is highly desirable. Here, we present an observation toward developing such a method, which is based on monitoring a change in water absorption by infrared spectroscopy. Infrared spectroscopy has high sensitivity for water, and changes in its hydrogen bond pattern can be observed. We studied absorption changes of water upon the addition of phosphenolpyruvate or Mg2+ to pyruvate kinase. In each case, there is a decrease in the absorption of water in the 3000-3100 cm(-1) region on the low wavenumber side of the OH stretching vibration when a ligand binds to the protein. Our results suggest that the weaker water absorption is due to the release of protein-bound water into bulk water during ligand binding. This observation has high potential for drug development as well as for basic research because it can lead to a general method for detecting molecular association events that (i) is label-free, (ii) works with both binding partners being in aqueous solution, and (iii) is based on a universal process that takes place in all binding events.

  • 41. Kunnus, Kristjan
    et al.
    Josefsson, Ida
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum.
    Schreck, Simon
    Quevedo, Wilson
    Miedemaa, Piter S.
    Techert, Simone
    de Groot, Frank M. F.
    Odelius, Michael
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum.
    Wernet, Philippe
    Föhlisch, Alexander
    From Ligand Fields to Molecular Orbitals: Probing the Local Valence Electronic Structure of Ni2+ in Aqueous Solutions with Resonant Inelastic X-ray Scattering2013Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 117, s. 16512-16521Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Bonding of the Ni2+(aq) complex is investigated with an unprecedented combination of resonant inelastic X-ray scattering (RIXS) measurements and ab initio calculations at the Ni L absorption edge. The spectra directly reflect the relative energies of the ligand-field and charge-transfer valence-excited states. They give element-specific access with atomic resolution to the ground-state electronic structure of the complex and allow quantification of ligand-field strength and 3d–3d electron correlation interactions in the Ni2+(aq) complex. The experimentally determined ligand-field strength is 10Dq = 1.1 eV. This and the Racah parameters characterizing 3d–3d Coulomb interactions B = 0.13 eV and C = 0.42 eV as readily derived from the measured energies match very well with the results from UV–vis spectroscopy. Our results demonstrate how L-edge RIXS can be used to complement existing spectroscopic tools for the investigation of bonding in 3d transition-metal coordination compounds in solution. The ab initio RASPT2 calculation is successfully used to simulate the L-edge RIXS spectra.

  • 42. Kunnus, Kristjan
    et al.
    Zhang, Wenkai
    Delcey, Mickael G.
    Pinjari, Rahul V.
    Miedema, Piter S.
    Schreck, Simon
    Quevedo, Wilson
    Schroeder, Henning
    Foehlisch, Alexander
    Gaffney, Kelly J.
    Lundberg, Marcus
    Odelius, Michael
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum.
    Wernet, Philippe
    Viewing the Valence Electronic Structure of Ferric and Ferrous Hexacyanide in Solution from the Fe and Cyanide Perspectives2016Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 120, nr 29, s. 7182-7194Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The valence-excited states of ferric and ferrous hexacyanide ions in aqueous solution were mapped by resonant inelastic X-ray scattering (RIXS) at the Fe L-2,L-3 and N K edges. Probing of both the central Fe and the ligand N atoms enabled identification of the metal-and ligand-centered excited states, as well as ligand-to-metal and metal-to-ligand charge-transfer excited states. Ab initio calculations utilizing the RASPT2 method were used to simulate the Fe L-2,L-3-edge RIXS spectra and enabled quantification of the covalencies of both occupied and empty orbitals of pi and sigma symmetry. We found that pi back-donation in the ferric complex is smaller than that in the ferrous complex. This is evidenced by the relative amounts of Fe 3d character in the nominally 2 pi CN- molecular orbital of 7% and 9% in ferric and ferrous hexacyanide, respectively. Utilizing the direct sensitivity of Fe L-3-edge RIXS to the Fe 3d character in the occupied molecular orbitals, we also found that the donation interactions are dominated by sigma bonding. The latter was found to be stronger in the ferric complex, with an Fe 3d contribution to the nominally 5 sigma CN- molecular orbitals of 29% compared to 20% in the ferrous complex. These results are consistent with the notion that a higher charge at the central metal atom increases donation and decreases back-donation.

  • 43.
    Liao, Rong-Zhen
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Yu, Jian-Guo
    Himo, Fahmi
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Reaction Mechanism of the Trinuclear Zinc Enzyme Phospholipase C: A Density Functional Theory Study2010Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 114, nr 7, s. 2533-2540Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Phosphatidylcholine-preferring phospholipase C is a trinuclear zinc-dependent phosphodiesterase, catalyzing the hydrolysis of choline phospholipids. In the present study, density functional theory is used to investigate the reaction mechanism of this enzyme. Two possible mechanistic scenarios were considered with a model of the active site designed on the basis of the high resolution X-ray crystal structure of the native enzyme. The calculations show that a Zn1 and Zn3 bridging hydroxide rather than a Zn1 coordinated water molecule performs the nucleophilic attack on the phosphorus center. Simultaneously, Zn2 activates a water molecule to protonate the leaving group. In the following step, the newly generated Zn2 bound hydroxide makes the reverse attack, resulting in the regeneration of the bridging hydroxide. The first step is calculated to be rate-limiting with a barrier of 17.3 kcal/mol, in good agreement with experimental kinetic studies. The zinc ions are suggested to orient the substrate for nucleophilic attack and provide electrostatic stabilization to the dianionic penta-coordinated trigonal bipyramidal transition states, thereby lowering the barrier.

  • 44.
    Liebau, Jobst
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Mäler, Lena
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Immersion Depths of Lipid Carbons in Bicelles Measured by Paramagnetic Relaxation Enhancement2017Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 121, nr 32, s. 7660-7670Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Myriads of biological processes occur in or at cellular lipid membranes. Knowledge about the localization of proteins, lipids, and other molecules within biological membranes is thus crucial for the understanding of such processes. Here, we present a method to determine the immersion depths of lipid carbon atoms in membranes by paramagnetic relaxation enhancement (PRE) caused by the presence of doxylated lipids. As membrane mimetics, we employ small isotropic bicelles made of synthetic lipids and of natural Escherichia coli phospholipid extract. Bicelles are particularly suitable for solution state NMR since they maintain a lipid bilayer while they are at the same time amenable to solution state NMR experiments. PREs were measured in the presence of different doxylated lipids with the nitroxide radical located in the headgroup and at various positions in the acyl chain. Theoretical PREs were calculated assuming a simple bicelle model using the Solomon–Bloembergen equations. Immersion depths of the lipid carbon atoms were obtained by a least-squares fit of the theoretical to the experimental PREs. The carbon immersion depths correspond well to results obtained by other methods and differences do not exceed 3–5 Å. This means that the method presented here provides sufficient resolution to distinguish the localization of carbons in different regions of the lipid bilayer, despite considerable simplifications of the underlying theory. These simplifications include a simple form of the spectral density function, which we find is sufficient to reliably determine immersion depths. A more complicated spectral density function that includes bicelle, lipid, and local motions may only improve the results if its parametrization is good enough. The approach presented here may be extended to the determination of protein localization in membranes employing realistic membrane mimetics like the bicelles made of E. coli phospholipid extract used here.

  • 45.
    Lundberg, Marcus
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum.
    Siegbahn, Per E.M.
    Optimized Spin Crossings and Transition States for Short-range Electron Transfer in Transition Metal Dimers2005Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 109, nr 20, s. 10513-10520Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Electron-transfer reactions in eight mixed-valence manganese dimers are studied using B3LYP. One of the dimers is a model of the active site of manganese catalase, while another represents a basic building block of the oxygen-evolving complex in photosystem II. The adiabatic reactions are characterized by fully optimized transition states where the single imaginary frequency represents the electron-transfer coordinate. When there is antiferromagnetic coupling between different high-spin centers, electron transfer must be accompanied by a spin transition. Spin transitions are characterized by minimum-energy crossing points between spin surfaces. Three reaction mechanisms have been investigated. First, a single-step reaction where spin flip is concerted with electron transfer. Second, an initial transition to a center with intermediate spin that can be followed by electron transfer. Third, an initial transition to a ferromagnetic state from which the electron can be transferred adiabatically. The complexes prefer the third route with rate-determining barriers ranging from 5.7 kcal/mol to 17.2 kcal/mol for different complexes. The origins of these differences are discussed in terms of oxidation states and ligand environments. Many DFT functionals overestimate charge-transfer interactions, but for the present complexes, the error should be limited because of short Mn−Mn distances

  • 46. Lundborg, Magnus
    et al.
    Lindahl, Erik
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik. Royal Institute of Technology, Sweden.
    Automatic GROMACS Topology Generation and Comparisons of Force Fields for Solvation Free Energy Calculations2015Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 119, nr 3, s. 810-823Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Free energy calculation has long been an important goal for molecular dynamics simulation and force field development, but historically it has been challenged by limited performance, accuracy, and creation of topologies for arbitrary small molecules. This has made it difficult to systematically compare different sets of parameters to improve existing force fields, but in the past few years several authors have developed increasingly automated procedures to generate parameters for force fields such as Amber, CHARMM, and OPLS. Here, we present a new framework that enables fully automated generation of GROMACS topologies for any of these force fields and an automated setup for parallel adaptive optimization of high-throughput free energy calculation by adjusting lambda point placement on the fly. As a small example of this automated pipeline, we have calculated solvation free energies of 50 different small molecules using the GAFF, OPLS-AA, and CGenFF force fields and four different water models, and by including the often neglected polarization costs, we show that the common charge models are somewhat underpolarized.

  • 47.
    Maliniak, Arnold
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för fysikalisk kemi, oorganisk kemi och strukturkemi.
    Dahlberg, Martin
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för fysikalisk kemi, oorganisk kemi och strukturkemi.
    Molecular dynamics simulations of cardiolipin bilayers2008Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 112, nr 37, s. 11655-11663Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cardiolipin is a key lipid component in the inner mitochondrial membrane, where the lipid is involved in energy production, cristae structure, and mechanisms in the apoptotic pathway. In this article we used molecular dynamics computer simulations to investigate cardiolipin and its effect on the structure of lipid bilayers. Three cardiolipin/POPC bilayers with different lipid compositions were simulated: 100, 9.2, and 0% cardiolipin. We found strong association of sodium counterions to the carbonyl groups of both lipid types, leaving in the case of 9.2% cardiolipin virtually no ions in the aqueous compartment. Although binding occurred primarily at the carbonyl position, there was a preference to bind to the carbonyl groups of cardiolipin. Ion binding and the small headgroup of cardiolipin gave a strong ordering of the hydrocarbon chains. We found significant effects in the water dipole orientation and water dipole potential which can compensate for the electrostatic repulsion that otherwise should force charged lipids apart. Several parameters relevant for the molecular structure of cardiolipin were calculated and compared with results from analyses of coarse-grained simulations and available X-ray structural data.

  • 48.
    Mandal, Paulami
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Eremina, Nadejda
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Barth, Andreas
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Formation of Two Different Types of Oligomers in the Early Phase of pH-Induced Aggregation of the Alzheimer A beta(12-28) Peptide2012Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 116, nr 41, s. 12389-12397Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The early phase in the aggregation process of the Alzheimer's peptide A beta(12-28) with both protected and unprotected ends was studied by time-resolved infrared spectroscopy and circular dichroism spectroscopy. Aggregation in the time-resolved experiments was initiated by a rapid pH drop caused by the photolysis of 1-(2-nitrophenyl)ethyl sulfate (caged sulfate). The infrared spectra indicate two different types of aggregates from both versions of the A beta(12-28) peptide. One type has small and/or twisted beta sheets with a beta-sheet band at 1627 cm(-1), They form fast (within 60 ms), presumably from initial aggregates, and their spectral signature is consistent with a beta-barrel structure. The other type arises relatively slowly from unstructured monomers on the seconds-to-minutes time scale and forms at lower pH than the first type. These beta sheets are antiparallel, planar, and large and show an absorption band at 1622 cm(-1) that shifts to 1617 cm(-1) in 12 min with most of the shift occurring in 10 s.

  • 49.
    Manta, Bianca
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Raushel, Frank M.
    Himo, Fahmi
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Reaction Mechanism of Zinc-Dependent Cytosine Deaminase from Escherichia coli: A Quantum-Chemical Study2014Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 118, nr 21, s. 5644-5652Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The reaction mechanism of cytosine deaminase from Escherichia coli is studied using density functional theory. This zinc-dependent enzyme catalyzes the deamination of cytosine to form uracil and ammonia. The calculations give a detailed description of the catalytic mechanism and establish the role of important active-site residues. It is shown that Glu217 is essential for the initial deprotonation of the metal-bound water nucleophile and the subsequent protonation of the substrate. It is also demonstrated that His246 is unlikely to function as a proton shuttle in the nucleophile activation step, as previously proposed. The steps that follow are nucleophilic attack by the metal-bound hydroxide, protonation of the leaving group assisted by Asp313, and C-N bond cleavage. The calculated overall barrier is in good agreement with the experimental findings. Finally, the calculations reproduce the experimentally determined inverse solvent deuterium isotope effect, which further corroborates the suggested reaction mechanism.

  • 50.
    Mariedahl, Daniel
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum.
    Perakis, Fivos
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum.
    Späh, Alexander
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum.
    Pathak, Harshad
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum.
    Kim, Kyung Hwan
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum.
    Camisasca, Gaia
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum.
    Schlesinger, Daniel
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljövetenskap och analytisk kemi.
    Benmore, Chris
    Pettersson, Lars Gunnar Moody
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum.
    Nilsson, Anders
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum.
    Arnann-Winkel, Katrin
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum.
    X-ray Scattering and O-O Pair-Distribution Functions of Amorphous Ices2018Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 122, nr 30, s. 7616-7624Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The structure factor and oxygen-oxygen pair distribution functions of amorphous ices at liquid nitrogen temperature (T = 77 K) have been derived from wide-angle X-ray scattering (WAXS) up to interatomic distances of r = 23 angstrom, where local structure differences between the amorphous ices can be seen for the entire range. The distances to the first coordination shell for low-, high-, and very-high-density amorphous ice (LDA, HDA, VHDA) were determined to be 2.75, 2.78, and 2.80 angstrom, respectively, with high accuracy due to measurements up to a large momentum transfer of 23 angstrom(-1). Similarities in pair-distribution functions between LDA and supercooled water at 254.1 K, HDA and liquid water at 365.9 K, and VHDA and high-pressure liquid water were found up to around 8 angstrom, but beyond that at longer distances, the similarities were lost. In addition, the structure of the high-density amorphous ices was compared to high-pressure crystalline ices IV, IX, and XII, and conclusions were drawn about the local ordering.

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