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1.
  • Lyubartsev, Alexander P., et al. (author)
  • Force Field Development for Lipid Membrane Simulations
  • 2016
  • In: Biochimica et Biophysica Acta - Biomembranes. - : Elsevier BV. - 0005-2736 .- 1879-2642. ; 1858:10, s. 2483-2497
  • Journal article (peer-reviewed)abstract
    • With the rapid development of computer power and wide availability of modelling software computer simulations of realistic models of lipid membranes, including their interactions with various molecular species, polypeptides and membrane proteins have become feasible for many research groups. The crucial issue of the reliability of such simulations is the quality of the force field, and many efforts, especially in the latest several years, have been devoted to parametrization and optimization of the force fields for biomembrane modelling. In this review, we give account of the recent development in this area, covering different classes of force fields, principles of the force field parametrization, comparison of the force fields, and their experimental validation. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Rog.
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2.
  • Lyubartsev, Alexander P., et al. (author)
  • Recent development in computer simulations of lipid bilayers
  • 2011
  • In: Soft Matter. - : Royal Society of Chemistry (RSC). - 1744-683X .- 1744-6848. ; 7:1, s. 25-39
  • Research review (peer-reviewed)abstract
    • Rapid development of computer power during the last decade has made molecular simulations of lipid bilayers feasible for many research groups, which, together with the growing general interest in investigations of these very important biological systems has lead to tremendous increase of the number of research on the computational modeling of lipid bilayers. In this review, we give account of the recent progress in computer simulations of lipid bilayers covering mainly the period of the last 5 years, and covering several selected subjects: development of the force fields for lipid bilayer simulations, studies of the role of lipid unsaturation, the effect of cholesterol and other inclusions on properties of the bilayer, and use of coarse-grained models.
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3.
  • Lyubartsev, Alexander, 1962-, et al. (author)
  • Systematic coarse-graining of molecular models by the Newton inversion method
  • 2010
  • In: Faraday discussions. - 1359-6640 .- 1364-5498. ; 144, s. 43-56
  • Journal article (peer-reviewed)abstract
    • Systematic construction of coarse-grained molecular models from detailed atomistic simulations, and even from ab initio simulations is discussed. Atomistic simulations are first performed to extract structural information about the system, which is then used to determine effective potentials for a coarse-grained model of the same system. The statistical-mechanical equations expressing the canonical properties in terms of potential parameters can be inverted and solved numerically according to the iterative Newton scheme. In our previous applications, known as the Inverse Monte Carlo, radial distribution functions were inverted to reconstruct pair potential, while in a more general approach the targets can be other canonical averages. We have considered several examples of coarse-graining; for the united atom water model we suggest an easy way to overcome the known problem of high pressure. Further, we have developed coarse-grained models for L- and D-prolines, dissolved here in an organic solvent (dimethylsulfoxide), keeping their enantiomeric properties from the corresponding all-atom proline model. Finally, we have revisited the previously developed coarse-grained lipid model based on an updated all-atomic force field. We use this model in large-scale meso-scale simulations demonstrating spontaneous formation of different structures, such as vesicles, micelles, and multi-lamellar structures, depending on thermodynamical conditions.
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4.
  • Minhas, Vishal, et al. (author)
  • Modeling DNA Flexibility : Comparison of Force Fields from Atomistic to Multiscale Levels
  • 2020
  • In: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 124:1, s. 38-49
  • Journal article (peer-reviewed)abstract
    • Accurate parametrization of force fields (FFs) is of ultimate importance for computer simulations to be reliable and to possess a predictive power. In this work, we analyzed, in multi-microsecond simulations of a 40-base-pair DNA fragment, the performance of four force fields, namely, the two recent major updates of CHARMM and two from the AMBER family. We focused on a description of double-helix DNA flexibility and dynamics both at atomistic and at mesoscale level in coarse-grained (CG) simulations. In addition to the traditional analysis of different base-pair and base-step parameters, we extended our analysis to investigate the ability of the force field to parametrize a CG DNA model by structure-based bottom-up coarse-graining, computing DNA persistence length as a function of ionic strength. Our simulations unambiguously showed that the CHARMM36 force field is unable to preserve DNA's structural stability at over-microsecond time scale. Both versions of the AMBER FF, parmbsc0 and parmbsc1, showed good agreement with experiment, with some bias of parmbsc0 parameters for intermediate A/B form DNA structures. The CHARMM27 force field provides stable atomistic trajectories and overall (among the considered force fields) the best fit to experimentally determined DNA flexibility parameters both at atomistic and at mesoscale level.
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5.
  • Mirzoev, Alexander, 1984-, et al. (author)
  • Effective solvent mediated potentials of Na+ and Cl− ions in aqueous solution : temperature dependence
  • 2011
  • In: Physical Chemistry, Chemical Physics - PCCP. - 1463-9076 .- 1463-9084. ; :13, s. 5722-5727
  • Journal article (peer-reviewed)abstract
    • The effective solvent-mediated potentials for Na+ and Cl− ions in aqueous solution were calculated in a wide range of temperatures from 0 to 100 °C. The potentials have been determined using the inverse Monte Carlo approach, from the ion–ion radial distribution functions computed in 50 ns molecular dynamics simulations of ions and explicit water molecules. We further separated the effective potentials into a short-range part and an electrostatic long-range part represented by a coulombic potential with some dielectric permittivity. We adjusted the value of the dielectric permittivity to provide the fastest possible decay of the short-range potentials at larger distances. The obtained temperature dependence of the dielectric permittivity follows well the experimental data. We show also that the largest part of the temperature dependence of the effective potentials can be attributed to the temperature-dependent dielectric permittivity.
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6.
  • Mirzoev, Alexander, 1984-, et al. (author)
  • MagiC : Software Package for Multiscale Modeling
  • 2013
  • In: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 9:3, s. 1512-1520
  • Journal article (peer-reviewed)abstract
    • We present software package MagiC, which is designed to perform systematic structure-based coarse graining of molecular models. The effective pairwise potentials between coarse-grained sites of low-resolution molecular models are constructed to reproduce structural distribution functions obtained from the modeling of the system in a high resolution (atomistic) description. The software supports coarse-grained tabulated intramolecular bond and angle interactions, as well as tabulated nonbonded interactions between different site types in the coarse-grained system, with the treatment of long-range electrostatic forces by the Ewald summation. Two methods of effective potential refinement are implemented: iterative Boltzmann inversion and inverse Monte Carlo, the latter accounting for cross-correlations between pair interactions. MagiC uses its own Metropolis Monte Carlo sampling engine, allowing parallel simulation of many copies of the system with subsequent averaging of the properties, which provides fast convergence of the method with nearly linear scaling at parallel execution.
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7.
  • Mirzoev, Alexander, et al. (author)
  • Magic v.3 : An integrated software package for systematic structure-based coarse-graining
  • 2019
  • In: Computer Physics Communications. - : Elsevier BV. - 0010-4655 .- 1879-2944. ; 237, s. 263-273
  • Journal article (peer-reviewed)abstract
    • Molecular simulations of many phenomena related to biomolecular systems, soft matter and nanomaterials require consideration of length scales above 10 nm and time scales longer than 1 mu s, which necessitates the use of coarse-grained (low resolution) models, where each site of the model represents a group of atoms, and where the solvent is often omitted. Our software package MagiC is designed to perform systematic structure-based coarse-graining of molecular models, in which the effective pairwise potentials between coarse-grained sites of low-resolution molecular models are constructed to reproduce structural distribution functions obtained from modeling of systems in a high resolution (atomistic) description. The software takes as input atomistic trajectories generated by an external molecular dynamics package, and produce as an output interaction potentials for coarse-grained models which can be directly used in a coarse-grained simulations package. Here we present a major update (v.3) of the software with substantially improved functionality, compatibility with several major atomistic and coarse-grained simulations packages (GROMACS, LAMMPS, GALAMOST), analysis suite with graphical possibilities, diagnostics, documentation. We describe briefly the coarse-graining methodology, the structure of the software, describe users actions, and illustrate the whole process with two complex examples: cholesterol containing lipid bilayers and condensation of DNA caused by multivalent ions. Program summary Program Title: MagiC Program Files doi : http://dx.doi.org/10.17632/9gnfxyshj8.1 Licensing provisions: GPLv3 Programming language: Fortran, Python Nature of problem: Systematic bottom-up multiscale modeling is a complex multi-stage process, in which results of simulations of a high-resolution (atomistic) model are used to construct a low resolution (coarse-grained) model, providing the same structural properties for the coarse-grained system as for the high-resolution system. Within the approach, structural properties of the high-resolution model are computed in terms of radial distribution functions and distributions of intramolecular degrees of freedom. Then the inverse problem is solved, in which the interaction potentials for the low-resolution model are determined which provide distribution functions coinciding with those obtained in the high-resolution simulations. The low-resolution model can be then used for simulations of the same system on larger length and time-scale. Solution method: The presented software package implements all stages of the systematic structure-based coarse-graining. It works as an integrated pipeline, giving the user ability to easily derive a coarse-grained model for a multicomponent complex molecular system and then use it for large-scale simulations. MagiC implements two approaches to solve the inverse problem: (i) the Inverse Monte Carlo method in which the inverse problem is solved using the Newton-Raphson method, with inversion of the Jacobian for the discretized relationship between interaction potentials and structural distribution functions; and (ii) the Iterative Boltzmann approach in which the inverse problem is solved using approximative relationships neglecting correlations between different degrees of freedom. The inverse solver includes also variational Inverse Monte Carlo approach when some of the coarse-grained potentials are fixed while others vary in order to fit the whole set of reference distribution functions. Additional comments: The MagiC main module can be also used for conventional Monte Carlo simulations of molecular systems described by tabulated pairwise potentials in the canonical ensemble.
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8.
  • Mirzoev, Alexander, 1984- (author)
  • Multiscale simulations of soft matter: systematic structure-based coarse-graining approach
  • 2013
  • Doctoral thesis (other academic/artistic)abstract
    • The soft matter field considers a wide class of objects such as liquids, polymers, gels, colloids, liquid crystals and biological macromolecules, which have complex internal structure and conformational flexibility leading to phenomena and properties having multiple spacial and time scales. Existing computer simulation methods are able to cover these scales, but with different resolutions, and ability to link them together performing a multiscale simulation is highly desirable.The present work addresses systematic multiscaling approach for soft matter studies, using structure-based coarse-graining (CG) methods such as iterative Boltzmann inversion and inverse Monte Carlo. A new software package MagiC implementing these methods is introduced. The software developed for the purpose of effective CG potential derivation is applied for ionic water solution and for water solution of DMPC lipids. A thermodynamic transferability of the obtained potentials is studied.The effective inter-ionic solvent mediated potentials derived for NaCl successfully reproduce structural properties obtained in explicit solvent simulation, which indicates the perspectives of using the structure-based coarse-graining for studies of ion-DNA and other polyelectrolytes systems. The potentials have temperature dependence, dominated mostly by the electrostatic long-range part which can be described by temperature dependent effective dielectric permittivity, leaving the short-range part of the potential thermodynamically transferable.For CG simulations of lipids a 10-bead water-free model of dimyristoylphosphatidylcholine is introduced. Four atomistic reference systems, having different lipid/water ratio are used to derive the effective bead-bead potentials, which are used for subsequent coarse-grained simulations of lipid bilayer. A significant influence of lipid/water ratio in the reference system on the properties of the simulated bilayers is noted, however it can be softened by additional angle-bending interactions. At the same time the obtained bilayers have stable structure with correct density profiles. The model provides acceptable agreement between properties of coarse-grained and atomistic bilayer, liquid crystal - gel phase transition with temperature change, as well as realistic self-aggregation behavior, which results in formation of bilayer, bicell or vesicle from a dispersed lipid solution in a large-scale simulation.
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9.
  • Mirzoev, Alexander, et al. (author)
  • Systematic Implicit Solvent Coarse Graining of Dimyristoylphosphatidylcholine Lipids
  • 2014
  • In: Journal of Computational Chemistry. - : Wiley. - 0192-8651 .- 1096-987X. ; 35:16, s. 1208-1218
  • Journal article (peer-reviewed)abstract
    • We have used systematic structure-based coarse graining to derive effective site-site potentials for a 10-site coarse-grained dimyristoylphosphatidylcholine (DMPC) lipid model and investigated their state point dependence. The potentials provide for the coarse-grained model the same site-site radial distribution functions, bond and angle distributions as those computed in atomistic simulations carried out at four different lipid-water molar ratios. It was shown that there is a non-negligible dependence of the effective potentials on the concentration at which they were generated, which is also manifested in the properties of the lipid bilayers simulated using these potentials. Thus, effective potentials computed at low lipid concentration favor to more condensed and ordered structure of the bilayer with lower average area per lipid, while potentials obtained at higher lipid concentrations provide more fluid-like structure. The best agreement with the reference data and experiment was achieved using the set of potentials derived from atomistic simulations at 1:30 lipid:water molar ratio providing fully saturated hydration of DMPC lipids. Despite theoretical limitations of pairwise coarse-grained potentials expressed in their state point dependence, all the resulting potentials provide a stable bilayer structure with correct partitioning of different lipid groups across the bilayer as well as acceptable values of the average lipid area, compressibility and orientational ordering. In addition to bilayer simulations, the model has proven its robustness in modeling of self-aggregation of lipids from randomly dispersed solution to ordered bilayer structures, bicelles, and vesicles.
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10.
  • Mirzoev, Alexander, 1984-, et al. (author)
  • Systematic implicit solvent coarse graining of DMPC lipids
  • Journal article (peer-reviewed)abstract
    • A 10-site coarse-grained implicit solvent model of DMPC phospholipid is developed with effective solvent-mediated potentials derived using the inverse Monte Carlo method. The potentials providing for the coarse-grained model the same site-site RDFs, bond and angle distributions as those computed in atomistic simulations were computed for four different lipid-water molar ratios.It was shown that there is a significant concentration dependence for both effective potentials and properties of lipid bilayers simulated using these potentials. Thus, effective potentials computed at low lipid concentration favour to more condensed and ordered structure of the bilayer with lower average area per lipid, while potentials obtained at higher lipid concentrations provide more fluid-like structure. Introduction of bending angle interaction into coarse-grained model makes effective potentials somewhat less concentration-dependent. The best agreement with the reference data and experiment was achieved using the set of potentials derived from atomistic simulations at 1:30 lipid:water molar ratio providing full hydration of DMPC lipids in bilayer. Despite theoretical limitations of the structure-based approach expressed in state point dependence of the effective potentials, all the resulting potentials provide a stable bilayer structure with correct partitioning of different lipid groups across the bilayer as well as acceptable values of the average lipid area and compressibility. Another important property demonstrated by the model is liquid/gel phase transition observed at lowering the temperature. In addition to bilayer simulations, the model has proven its robustness in modeling of self-aggregation of lipids from randomly dispersed solution to ordered bilayer structures, bicells and vesicles.
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11.
  • Rabinovich, Alexander L., et al. (author)
  • Bond orientation properties in lipid molecules of membranes : molecular dynamics simulations
  • 2014
  • In: 25th IUPAP Conference on Computational Physics (CCP2013). - : Institute of Physics (IOP).
  • Conference paper (peer-reviewed)abstract
    • Atomistic molecular dynamics simulations have been carried out for 16 different fully hydrated phosphatidylcholine lipid bilayers, having 16 or 18 carbon atoms in fully saturated sn-1 chain and from 18 to 22 carbon atoms in sn-2 chain with different degree of unsaturation, with the purpose to investigate the effect of unsaturation on physical properties of lipid bilayers. Special attention has been paid to profiles of C-C and C-H bond order parameters of lipid molecules and the orientational fluctuations of these bond vectors. It was shown that the study of anisotropy degree of bond orientations probability distributions allows distinguishing extended regions with different types of angular fluctuations of bonds in a membrane formed by lipid molecules with unsaturated chains.
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12.
  • Rabinovich, Alexander L., et al. (author)
  • Unperturbed hydrocarbon chains and liquid phase bilayer lipid chains : a computer simulation study
  • 2018
  • In: European Biophysics Journal. - : Springer Science and Business Media LLC. - 0175-7571 .- 1432-1017. ; 47:2, s. 109-130
  • Journal article (peer-reviewed)abstract
    • In this work, the properties of saturated and unsaturated fatty acid acyl chains 16:0, 18:0, 18:1(n-9)cis, 18:2(n-6)cis, 18:3(n-3)cis, 18:4(n-3)cis, 18:5(n-3)cis, 20:4(n-6)cis, 20:5(n-3)cis and 22:6(n-3)cis in a bilayer liquid crystalline state and similar hydrocarbon chains (with CH terminal groups instead of C=O groups) in the unperturbed state characterised by a lack of long-range interaction were investigated. The unperturbed hydrocarbon chains were modelled by Monte Carlo simulations at temperature K; sixteen fully hydrated homogeneous liquid crystalline phosphatidylcholine bilayers containing these chains were studied by molecular dynamics simulations at the same temperature. To eliminate effects of the simulation parameters, the molecular dynamics and Monte Carlo simulations were carried out using the same structural data and force field coefficients. From these computer simulations, the average distances between terminal carbon atoms of the chains (end-to-end distances) were calculated and compared. The trends in the end-to-end distances obtained for the unperturbed chains were found to be qualitatively similar to those obtained for the same lipid chains in the bilayers. So, for understanding of a number of processes in biological membranes (e.g., changes in fatty acid composition caused by environmental changes such as temperature and pressure), it is possible to use, at least as a first approximation, the relationships between the structure and properties for unperturbed or isolated hydrocarbon chains.
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13.
  • Santosh, Mysore S., et al. (author)
  • Molecular Dynamics Investigation of Dipeptide - Transition Metal Salts in Aqueous Solutions
  • 2010
  • In: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 114:49, s. 16632-16640
  • Journal article (peer-reviewed)abstract
    • Molecular dynamics (MD) simulations of glycylglycine dipeptide with transition metal ions (Mn2+, Fe2+, Co2+, Ni2+, Cu2+, and Zn2+) in aqueous solutions have been carried out to get an insight into the solvation structure, intermolecular interactions, and salt effects in these systems. The solvation structure and hydrogen bonding were described in terms of radial distribution function (RDF) and spatial distribution function (SDF). The dynamical properties of the solvation structure were also analyzed in terms of diffusion and residence times. The simulation results show the presence of a well-defined first hydration shell around the dipeptide, with water molecules forming hydrogen bonds to the polar groups of the dipeptide. This shell is, however, affected by the strong electric field of divalent metal ions, which at higher ion concentrations lead to the shift in the dipeptide−water RDFs. Higher salt concentrations lead also to increased residence times and slower diffusion rates. In general, smaller ions (Cu2+, Zn2+) demonstrate stronger binding to dipeptide than the larger ones (Fe2+, Mn2+). Simulations do not show any stronger association of peptide molecules indicating their dissolution in water. The above results may be of potential interest to future researchers on these molecular interactions.
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14.
  • Santosh, Mysore Sridhar, et al. (author)
  • Solute-Solvent Interactions in Aqueous Glycylglycine-CuCl(2) Solutions : Acoustical and Molecular Dynamics Perspective
  • 2011
  • In: Journal of Solution Chemistry. - : Springer Science and Business Media LLC. - 0095-9782 .- 1572-8927. ; 40:9, s. 1657-1671
  • Journal article (peer-reviewed)abstract
    • Acoustical and molecular dynamics studies were carried out to understand the various interactions present in glycylglycine-CuCl(2) aqueous solutions. Amongst these interactions, hydrogen bonding and solute-solvent interactions have been highlighted in this study. The radial distribution function (RDF) was used to investigate solution structure and hydration parameters. Binding of Cu(2+) with various polar peptide atoms reveals the nature and degree of binding. The formation of complex clusters between glycylglycine and water molecules increases the relaxation time. The first hydration shell considerably influences the structure of the second shell, facilitating the formation of an ordered hydrogen bonded network. Both experimental and theoretical results have proved to be efficient in analyzing the behavior of molecules and to give a clear idea on molecular interactions in solutions.
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15.
  • Sun, Tiedong, et al. (author)
  • A Bottom-Up Coarse-Grained Model for Nucleosome-Nucleosome Interactions with Explicit Ions
  • 2022
  • In: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 18:6, s. 3948-3960
  • Journal article (peer-reviewed)abstract
    • The nucleosome core particle (NCP) is a large complex of 145–147 base pairs of DNA and eight histone proteins and is the basic building block of chromatin that forms the chromosomes. Here, we develop a coarse-grained (CG) model of the NCP derived through a systematic bottom-up approach based on underlying all-atom MD simulations to compute the necessary CG interactions. The model produces excellent agreement with known structural features of the NCP and gives a realistic description of the nucleosome–nucleosome attraction in the presence of multivalent cations (Mg(H2O)62+ or Co(NH3)63+) for systems comprising 20 NCPs. The results of the simulations reveal structural details of the NCP–NCP interactions unavailable from experimental approaches, and this model opens the prospect for the rigorous modeling of chromatin fibers. 
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16.
  • Sun, Tiedong, et al. (author)
  • A multiscale analysis of DNA phase separation : from atomistic to mesoscale level
  • 2019
  • In: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 47:11, s. 5550-5562
  • Journal article (peer-reviewed)abstract
    • DNA condensation and phase separation is of utmost importance for DNA packing in vivo with important applications in medicine, biotechnology and polymer physics. The presence of hexagonally ordered DNA is observed in virus capsids, sperm heads and in dinoflagellates. Rigorous modelling of this process in all-atom MD simulations is presently difficult to achieve due to size and time scale limitations. We used a hierarchical approach for systematic multiscale coarse-grained (CG) simulations of DNA phase separation induced by the three-valent cobalt(III)-hexammine (CoHex(3+)). Solvent-mediated effective potentials for a CG model of DNA were extracted from all-atom MD simulations. Simulations of several hundred 100-bp-long CG DNA oligonucleotides in the presence of explicit CoHex(3+) ions demonstrated aggregation to a liquid crystalline hexagonally ordered phase. Following further coarse-graining and extraction of effective potentials, we conducted modelling at mesoscale level. In agreement with electron microscopy observations, simulations of an 10.2-kblong DNA molecule showed phase separation to either a toroid or a fibre with distinct hexagonal DNA packing. The mechanism of toroid formation is analysed in detail. The approach used here is based only on the underlying all-atom force field and uses no adjustable parameters and may be generalised to modelling chromatin up to chromosome size.
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17.
  • Sun, Tiedong, et al. (author)
  • All-Atom MD Simulation of DNA Condensation Using Ab lnitio Derived Force Field Parameters of Cobalt(III)-Hexammine
  • 2017
  • In: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 121:33, s. 7761-7770
  • Journal article (peer-reviewed)abstract
    • It is well established that the presence of the trivalent cobalt(III)-hexammine cation (CoHex(3+)) at submillimolar concentrations leads to bundling (condensation) of double stranded DNA molecules, which is caused by DNA DNA attraction induced by the multivalent counterions. However, the detailed mechanism of this process is still not fully understood. Furthermore, in all-atom molecular dynamics (MD) simulations, spontaneous aggregation of several DNA oligonucleotides in the presence of CoHex(3+) has previously not been, demonstrated. In order to obtain a rigorous description of CoHex(3+)-nucleic acid interactions and CoHex(3+)-induced DNA condensation to be used in MD siniulations, we have derived optimized force field parameters of the CoHex(3+) ion. They were obtained from Car Parrinello molecular dynamics simulation of a single CoHex3+ ion in the presence of 126 water molecules. The new set,of force field parameters reproduces the experimentally known transition of DNA from B- to A-form; and qualitatively describes changes of DNA and RNA persistence lengths. We then carried out a 2 mu s long atomistic simulation of four DNA oligomers each consisting of 36 base pairs in the presence of CoHex(3+). We demonstrate that, in this system, DNA molecules display attractive interactions and aggregate into bundle-like structures. This behavior depends critically on the details of the CoHex(3+) interaction with DNA. A control simulation with a similar setup but in the presence of Mg2+ does not induce DNA DNA attraction, which is also in agreement with experiment.
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18.
  • Sun, Tiedong, et al. (author)
  • Bottom-Up Coarse-Grained Modeling of DNA
  • 2021
  • In: Frontiers in Molecular Biosciences. - : Frontiers Media SA. - 2296-889X. ; 8
  • Research review (peer-reviewed)abstract
    • Recent advances in methodology enable effective coarse-grained modeling of deoxyribonucleic acid (DNA) based on underlying atomistic force field simulations. The so-called bottom-up coarse-graining practice separates fast and slow dynamic processes in molecular systems by averaging out fast degrees of freedom represented by the underlying fine-grained model. The resulting effective potential of interaction includes the contribution from fast degrees of freedom effectively in the form of potential of mean force. The pair-wise additive potential is usually adopted to construct the coarse-grained Hamiltonian for its efficiency in a computer simulation. In this review, we present a few well-developed bottom-up coarse-graining methods, discussing their application in modeling DNA properties such as DNA flexibility (persistence length), conformation, melting, and DNA condensation.
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19.
  • Agosta, Lorenzo, 1986- (author)
  • Atomistic simulations of structural and dynamical properties of liquids under geometric constraints
  • 2019
  • Doctoral thesis (other academic/artistic)abstract
    • The statistical-mechanical description of liquids represents a formidable problem in physic due to the absence of the analytical theory of the liquid state. Atomistic simulations represent a unique source of information in this respect and can be implemented in order address macroscopically measurable liquid properties, including its structure and dynamics, based on the information of the interactions between its constituent molecules. A particularly intriguing challenge is represented by the problem of studying liquids under geometric constraints like surfaces, or where the dimensionality is strongly suppressed like for liquids in 2 dimensions. Experimental measurements cannot access to these regions due to the resolution limitations. In this thesis the study of confined liquids is achieved by particle-based simulations at different level of theory. In particular 3 study cases are considered: the first is the characterization of solid-liquid interfaces. The problem of adsorbing surfaces is treated as a specific case of inorganic surfaces in contact with liquid water. TiO2, chosen as reference material, is studied in its polymorphic structures in aqueous conditions. The surface reactivity and its influence on the liquid structure is solved considering the quantum nature of the system. The mechanism of a solute adsorbing at the interface, considering the interfacial liquid properties, is also addressed. New advanced analysis tools for determining the structural and dynamical properties of water under a surface confinement and the thermodynamic associated to relative adsorption processes are developed. We are confident that this study will represent a mile stone for a systematic study of complex environments as bio-inorganic interfaces. As second case a liquid confined in a 2D surface is studied. Simple liquids having spherically symmetric interaction are very powerful in order to understand the relevant degrees of freedom that governs a certain physical process. Here we expand the definition of 2D hexatic phases to smectic systems in 3D. Finally the self-assembly of a triply periodic mesophase having a Fddd space symmetry group is fully characterized for a simple liquid. This phase can be thought as a geometrical reduction to a two-dimensional separation surface. The possibility of generating such complex network with simple particles, like in colloids, opens the frontiers for the exploration of new materials and applications.
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20.
  • Agosta, Lorenzo, et al. (author)
  • Diffusion and reaction pathways of water near fully hydrated TiO2 surfaces from ab initio molecular dynamics
  • 2017
  • In: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 147:2
  • Journal article (peer-reviewed)abstract
    • Ab initio molecular dynamics simulations are reported forwater-embedded TiO2 surfaces to determine the diffusive and reactive behavior at full hydration. A three-domain model is developed for six surfaces [rutile (110), (100), and (001), and anatase (101), (100), and (001)] which describes waters as hard (irreversibly bound to the surface), soft (with reduced mobility but orientation freedom near the surface), or bulk. The model explains previous experimental data and provides a detailed picture of water diffusion near TiO2 surfaces. Water reactivity is analyzed with a graph-theoretic approach that reveals a number of reaction pathways on TiO2 which occur at full hydration, in addition to direct water splitting. Hydronium (H3O+) is identified to be a key intermediate state, which facilitates water dissociation by proton hopping between intact and dissociated waters near the surfaces. These discoveries significantly improve the understanding of nanoscale water dynamics and reactivity at TiO2 interfaces under ambient conditions.
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21.
  • Agosta, Lorenzo, et al. (author)
  • Improved Sampling in Ab Initio-Based Free Energy Calculations of Amino Acids at Solid-Liquid Interfaces : A Tight-Binding Assessment on TiO2 Anatase (101)
  • Other publication (other academic/artistic)abstract
    • Atomistic simulations are powerful for probing molecules at bioinorganic interfaces and excellent complements to scarcely available experimental techniques. The free energy controls the adsorption behavior of molecules on nanosurfaces, and is therefore a quantity of particular importance. Advanced sampling techniques can efficiently explore the adsorption free energy landscape, but molecular simulations with classical (Newtownian) dynamics fail to capture charge transfer and polarization at the solid-liquid interface. First principle simulations do not suffer from this limitation but come with a heavy computational load. Here, we introduce an efficient protocol to explore the free energy of adsorption in the ab initio framework. This approach accurately models the complex phenomena at bio-inorganic surfaces on the nanoscale and properly samples the relevant thermodynamic properties. We present a case study of adsorption of the Lysine and Aspartate amino acids on the anatase (101) TiO2 surface with the tight binding method. The high values of the calculated adsorption free energies highlight the importance of a proper description of the electronic state for surface binding processes.
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22.
  • Agosta, Lorenzo, et al. (author)
  • Improved Sampling in Ab Initio Free Energy Calculations of Biomolecules at Solid-Liquid Interfaces : Tight-Binding Assessment of Charged Amino Acids on TiO2 Anatase (101)
  • 2020
  • In: Computation. - : MDPI AG. - 2079-3197. ; 8:1
  • Journal article (peer-reviewed)abstract
    • Atomistic simulations can complement the scarce experimental data on free energies of molecules at bio-inorganic interfaces. In molecular simulations, adsorption free energy landscapes are efficiently explored with advanced sampling methods, but classical dynamics is unable to capture charge transfer and polarization at the solid-liquid interface. Ab initio simulations do not suffer from this flaw, but only at the expense of an overwhelming computational cost. Here, we introduce a protocol for adsorption free energy calculations that improves sampling on the timescales relevant to ab initio simulations. As a case study, we calculate adsorption free energies of the charged amino acids Lysine and Aspartate on the fully hydrated anatase (101) TiO2 surface using tight-binding forces. We find that the first-principle description of the system significantly contributes to the adsorption free energies, which is overlooked by calculations with previous methods.
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23.
  • Atzori, Alessio, et al. (author)
  • Base sequence specificity of counterion binding to DNA : what can MD simulations tell us?
  • 2016
  • In: Canadian journal of chemistry (Print). - : Canadian Science Publishing. - 0008-4042 .- 1480-3291. ; 94:12, s. 1181-1188
  • Journal article (peer-reviewed)abstract
    • Nucleic acids are highly charged biopolymers whose secondary structure is strongly dependent on electrostatic interactions. Solvent molecules and ions are also believed to play an important role in mediating and directing both sequence recognition and interactions with other molecules, such as proteins and a variety of ligands. Therefore, to fully understand the biological functions of DNA, it is necessary to understand the interactions with the surrounding counterions. It is well known that monovalent counterions can bind to the minor groove of DNA with consecutive sequences of four, or more, adenine and thymine (A-tracts) with relatively long residence times. However, much less is known about their binding to the backbone and to the major groove. In this work, we used molecular dynamics simulations to both investigate the interactions between the backbone and major groove of DNA and one of its physiological counterions (Na+) and evaluate the relationship between these interactions and the nucleotide sequence. Three dodecamers, namely CGAAAATTTTCG, CGCTCTAGAGCG, and CGCGAATTCGCG, were simulated using the Toukan-Rahman flexible SPC water model and Smith and Dang parameters for Na+, revealing a significant sequence dependence on the ion binding to both backbone and major groove. In the absence of experimental data on the atomistic details of the studied interactions, the reliability of the results was evaluated performing the simulations with additional sets of potential parameters for ions and solvent, namely the A. qvist or the Joung and Cheatham ion parameters and the TIP3P water model. This allowed us to evaluate the results by verifying which features are preserved independently from the parameters adopted.
  •  
24.
  • B. Brant Carvalho, Paulo H., et al. (author)
  • Exploring High-Pressure Transformations in Low-Z (H2, Ne) Hydrates at Low Temperatures
  • 2022
  • In: Crystals. - : MDPI AG. - 2073-4352. ; 12:1
  • Journal article (peer-reviewed)abstract
    • The high pressure structural behavior of H-2 and Ne clathrate hydrates with approximate composition H-2/Ne center dot~4H(2)O and featuring cubic structure II (CS-II) was investigated by neutron powder diffraction using the deuterated analogues at ~95 K. CS-II hydrogen hydrate transforms gradually to isocompositional C-1 phase (filled ice II) at around 1.1 GPa but may be metastably retained up to 2.2 GPa. Above 3 GPa a gradual decomposition into C-2 phase (H-2 center dot H2O, filled ice I-c) and ice VIII' takes place. Upon heating to 200 K the CS-II to C-1 transition completes instantly whereas C-1 decomposition appears sluggish also at 200 K. C-1 was observed metastably up to 8 GPa. At 95 K C-1 and C-2 hydrogen hydrate can be retained below 1 GPa and yield ice II and ice I-c, respectively, upon complete release of pressure. In contrast, CS-II neon hydrate undergoes pressure-induced amorphization at 1.9 GPa, thus following the general trend for noble gas clathrate hydrates. Upon heating to 200 K amorphous Ne hydrate crystallizes as a mixture of previously unreported C-2 hydrate and ice VIII'.
  •  
25.
  • B. Brant Carvalho, Paulo H., 1990-, et al. (author)
  • Neutron scattering study of polyamorphic THF·17(H2O) : toward a generalized picture of amorphous states and structures derived from clathrate hydrates
  • 2023
  • In: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry. - 1463-9076 .- 1463-9084. ; 25:21, s. 14981-14991
  • Journal article (peer-reviewed)abstract
    • From crystalline tetrahydrofuran clathrate hydrate, THF-CH (THF·17H2O, cubic structure II), three distinct polyamorphs can be derived. First, THF-CH undergoes pressure-induced amorphization when pressurized to 1.3 GPa in the temperature range 77-140 K to a form which, in analogy to pure ice, may be called high-density amorphous (HDA). Second, HDA can be converted to a densified form, VHDA, upon heat-cycling at 1.8 GPa to 180 K. Decompression of VHDA to atmospheric pressure below 130 K produces the third form, recovered amorphous (RA). Results from neutron scattering experiments and molecular dynamics simulations provide a generalized picture of the structure of amorphous THF hydrates with respect to crystalline THF-CH and liquid THF·17H2O solution (∼2.5 M). Although fully amorphous, HDA is heterogeneous with two length scales for water-water correlations (less dense local water structure) and guest-water correlations (denser THF hydration structure). The hydration structure of THF is influenced by guest-host hydrogen bonding. THF molecules maintain a quasiregular array, reminiscent of the crystalline state, and their hydration structure (out to 5 Å) constitutes ∼23H2O. The local water structure in HDA is reminiscent of pure HDA-ice featuring 5-coordinated H2O. In VHDA, the hydration structure of HDA is maintained but the local water structure is densified and resembles pure VHDA-ice with 6-coordinated H2O. The hydration structure of THF in RA constitutes ∼18 H2O molecules and the water structure corresponds to a strictly 4-coordinated network, as in the liquid. Both VHDA and RA can be considered as homogeneous.
  •  
26.
  • B. Brant Carvalho, Paulo H., et al. (author)
  • Pressure-induced amorphization of noble gas clathrate hydrates
  • 2021
  • In: Physical Review B. - : American Physical Society. - 2469-9950 .- 2469-9969. ; 103:6
  • Journal article (peer-reviewed)abstract
    • The high-pressure structural behavior of the noble gas (Ng) clathrate hydrates Ar center dot 6.5 H2O and Xe center dot 7.2 H2O featuring cubic structures II and I, respectively, was investigated by neutron powder diffraction (using the deuterated analogues) at 95 K. Both hydrates undergo pressure-induced amorphization (PIA), indicated by the disappearance of Bragg diffraction peaks, but at rather different pressures, at 1.4 and above 4.0 GPa, respectively. Amorphous Ar hydrate can be recovered to ambient pressure when annealed at >1.5 GPa and 170 K and is thermally stable up to 120 K. In contrast, it was impossible to retain amorphous Xe hydrate at pressures below 3 GPa. Molecular dynamics (MD) simulations were used to obtain general insight into PIA of Ng hydrates, from Ne to Xe. Without a guest species, both cubic clathrate structures amorphize at 1.2 GPa, which is very similar to hexagonal ice. Filling of large-sized H cages does not provide stability toward amorphization for structure II, whereas filled small-sized dodecahedral D cages shift PIA successively to higher pressures with increasing size of the Ng guest. For structure I, filling of both kinds of cages, large-sized T and small-sized D, acts to stabilize in a cooperative fashion. Xe hydrate represents a special case. In MD, disordering of the guest hydration structure is already seen at around 2.5 GPa. However, the different coordination numbers of the two types of guests in the crystalline cage structure are preserved, and the state is shown to produce a Bragg diffraction pattern. The experimentally observed diffraction up to 4 GPa is attributed to this semicrystalline state.
  •  
27.
  • B. Brant Carvalho, Paulo H., et al. (author)
  • Structural investigation of three distinct amorphous forms of Ar hydrate
  • 2021
  • In: RSC Advances. - : Royal Society of Chemistry. - 2046-2069. ; 11:49, s. 30744-30754
  • Journal article (peer-reviewed)abstract
    • Three amorphous forms of Ar hydrate were produced using the crystalline clathrate hydrate Ar·6.5H2O (structure II, Fd3m, a ≈ 17.1 Å) as a precursor and structurally characterized by a combination of isotope substitution (36Ar) neutron diffraction and molecular dynamics (MD) simulations. The first form followed from the pressure-induced amorphization of the precursor at 1.5 GPa at 95 K and the second from isobaric annealing at 2 GPa and subsequent cooling back to 95 K. In analogy to amorphous ice, these amorphs are termed high-density amorphous (HDA) and very-high-density amorphous (VHDA), respectively. The third amorph (recovered amorphous, RA) was obtained when recovering VHDA to ambient pressure (at 95 K). The three amorphs have distinctly different structures. In HDA the distinction of the original two crystallographically different Ar guests is maintained as differently dense Ar–water hydration structures, which expresses itself in a split first diffraction peak in the neutron structure factor function. Relaxation of the local water structure during annealing produces a homogeneous hydration environment around Ar, which is accompanied with a densification by about 3%. Upon pressure release the homogeneous amorphous structure undergoes expansion by about 21%. Both VHDA and RA can be considered frozen solutions of immiscible Ar and water in which in average 15 and 11 water molecules, respectively, coordinate Ar out to 4 Å. The local water structures of HDA and VHDA Ar hydrates show some analogy to those of the corresponding amorphous ices, featuring H2O molecules in 5- and 6-fold coordination with neighboring molecules. However, they are considerably less dense. Most similarity is seen between RA and low density amorphous ice (LDA), which both feature strictly 4-coordinated H2O networks. It is inferred that, depending on the kind of clathrate structure and occupancy of cages, amorphous states produced from clathrate hydrates display variable local water structures.
  •  
28.
  • Barros Brant Carvalho, Paulo Henrique, et al. (author)
  • Neutron scattering study of polyamorphic THF ∙ (H2O)17 – toward a generalized picture of amorphous states and structures derived from clathrate hydrates
  • Other publication (other academic/artistic)abstract
    • From crystalline tetrahydrofuran clathrate hydrate, THF-CH (THF ∙ 17H2O, cubic structure II), three distinct polyamorphs can be derived. First, THF-CH undergoes pressure-induced amorphization when pressurized to 1.3 GPa in the temperature range 77–140 K to a form which, in analogy to pure ice, may be called high-density amorphous (HDA). Second, HDA can be converted to a densified form, very-HDA (VHDA), upon heat-cycling at 1.8 GPa to 180 K. Decompression of VHDA to atmospheric pressure below 130 K produces the third, recovered amorphous (RA) form. Results from a compilation of neutron scattering experiments and molecular dynamics simulations provide a generalized picture of the structure of amorphous THF hydrates with respect to crystalline THF-CH and liquid THF ∙ 17H2O solution (~2.5 M). The calculated density of (only in situ observable) HDA and VHDA at 2 GPa and 130 K is 1.287 and 1.328 g/cm3, respectively, whereas that of RA (at 1 atm) is 1.081 g/cm3. Although fully amorphous, HDA is heterogeneous with two length scales for water-water correlations (less dense local water structure) and guest-water correlations (denser THF hydration structure). The hydration structure of THF is influenced by guest-host hydrogen bonding. THF molecules maintain a quasiregular array, reminiscent of the crystalline state, and their hydration structure (out to 5 Å) constitutes ~23 H2O. The local water structure in HDA is reminiscent of pure HDA-ice, featuring 5-coordinated H2O. In VHDA, this structure is maintained but the local water structure is densified to resemble pure VHDA-ice with 6-coordinated H2O. The hydration structure of THF in RA constitutes ~18 H2O and the water structure corresponds to a strictly 4-coordinated network, as in the liquid. Both VHDA and RA can be considered as homogeneous, solid solutions of THF and water. The local water structure of water-rich (1:17) amorphous CHs resembles most that of the corresponding amorphous water ices when compared to guest-rich CHs, e.g., Ar ∙ ~6H2O. The proposed significance of different contributions of water local environments presents a simple view to justify neutron structure factor features.
  •  
29.
  • Botan, Alexandru, et al. (author)
  • Toward Atomistic Resolution Structure of Phosphatidylcholine Headgroup and Glycerol Backbone at Different Ambient Conditions
  • 2015
  • In: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 119:49, s. 15075-15088
  • Journal article (peer-reviewed)abstract
    • 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.
  •  
30.
  • Brandt, Erik G., et al. (author)
  • Molecular Dynamics Simulations of Adsorption of Amino Acid Side Chain Analogues and a Titanium Binding Peptide on the TiO2 (100) Surface
  • 2015
  • In: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 119:32, s. 18126-18139
  • Journal article (peer-reviewed)abstract
    • Adsorption profiles and adsorption free energies were determined for the side chain analogues of the 20 naturally occurring amino acids and a titanium binding peptide on the TiO2 (100) surface. Microsecond simulations with umbrella sampling and metadynamics were used to sample the free energy barriers associated with desolvation of strongly bound water molecules at the TiO2 surface. Polar and aromatic side chain analogues that hydrogen bond either to surface waters or directly to the metal oxide surface were found to be the strongest binders. Further, adsorption simulations of a 6 residue titanium binding peptide identified two binding modes on TiO2 (100). The peptide structure with lowest free energy was shown to be stabilized by a salt bridge between the end termini. A comparison between the free energies of the side chain analogues of the peptide sequence and the peptide itself shows that the free energy contributions are not additive. The simulations emphasize that tightly bound surface waters play a key role for peptide and protein structures when bound to inorganic surfaces in biological environments.
  •  
31.
  • Brandt, Erik G., et al. (author)
  • Reactive wetting properties of TiO2 nanoparticles predicted by ab initio molecular dynamics simulations
  • 2016
  • In: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 8:27, s. 13385-13398
  • Journal article (peer-reviewed)abstract
    • Small-sized wet TiO2 nanoparticles have been investigated by ab initio molecular dynamics simulations. Chemical and physical adsorption of water on the TiO2-water interface was studied as a function of water content, ranging from dry nanoparticles to wet nanoparticles with monolayer coverage of water. The surface reactivity was shown to be a concave function of water content and driven by surface defects. The local coordination number at the defect was identified as the key factor to decide whether water adsorption proceeds through dissociation or physisorption on the surface. A consistent picture of TiO2 nanoparticle wetting at the microscopic level emerges, which corroborates existing experimental data and gives further insight into the molecular mechanisms behind nanoparticle wetting. These calculations will facilitate the engineering of metal oxide nanoparticles with a controlled catalytic water activity.
  •  
32.
  • Brandt, Erik G., et al. (author)
  • Systematic Optimization of a Force Field for Classical Simulations of TiO2-Water Interfaces
  • 2015
  • In: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 119:32, s. 18110-18125
  • Journal article (peer-reviewed)abstract
    • Atomistic force field parameters were developed for the TiO2-water interface by systematic optimization with respect to experimentally determined crystal structures (lattice parameters) and surface thermodynamics (water adsorption enthalpy). Optimized force field parameters were determined for the two cases where TiO2 was modeled with or without covalent bonding. The nonbonded TiO2 model can be used to simulate different TiO2 phases, while the bonded TiO2 model is particularly useful for simulations of nanosized TiO2 and biomatter, including protein-surface and nanoparticle-biomembrane simulations. The procedure is easily generalized to parametrize interactions between other inorganic surfaces and biomolecules.
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33.
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34.
  • Bunta, Juraj, et al. (author)
  • Solvating, manipulating, damaging, and repairing DNA in a computer
  • 2007
  • In: International Journal of Quantum Chemistry. - New York : Wiley. - 0020-7608 .- 1097-461X. ; 107:2, s. 279-291
  • Journal article (peer-reviewed)abstract
    • This work highlights four different topics in modeling of DNA: (i) the importance of water and ions together with the structure and function of DNA; the hydration structure around the ions appears to be the determining factor in the ion coordination to DNA, as demonstrated in the results of our MD simulations; (ii) how MD simulations can be used to simulate single molecule manipulation experiments as a complement to reveal the structural dynamics of the studied biomolecules; (iii) how damaged DNA can be studied in computer simulations; and (iv) how repair of damaged DNA can be studied theoretically.
  •  
35.
  • Castro, Vasco, et al. (author)
  • NMR investigations of interactions between anesthetics and lipid bilayers
  • 2008
  • In: Biochimica et Biophysica Acta - Biomembranes. - : ELSEVIER SCIENCE BV. - 0005-2736 .- 1879-2642. ; 1178:11, s. 2604-2611
  • Journal article (peer-reviewed)abstract
    • Interactions between anesthetics (lidocaine and short chain alcohols) and lipid membranes formed by dimyristoylphosphatidylcholine (DMPC) were studied using NMR spectroscopy. The orientational order of lidocaine was investigated using deuterium NMR on a selectively labelled compound whereas segmental ordering in the lipids was probed by two-dimensional 1H–13C separated local field experiments under magic-angle spinning conditions. In addition, trajectories generated in molecular dynamics (MD) computer simulations were used for interpretation of the experimental results. Separate simulations were carried out with charged and uncharged lidocaine molecules. Reasonable agreement between experimental dipolar interactions and the calculated counterparts was observed. Our results clearly show that charged lidocaine affects significantly the lipid headgroup. In particular the ordering of the lipids is increased accompanied by drastic changes in the orientation of the P–N vector in the choline group.
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36.
  • Dong, Kun, et al. (author)
  • Structural Evidence for the Ordered Crystallites of Ionic Liquid in Confined Carbon Nanotubes
  • 2009
  • In: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 113:23, s. 10013-10020
  • Journal article (peer-reviewed)abstract
    • Ionic liquids (ILs) are a class of new green materials that have attracted extensive attention in recent decades. Many novel properties not evident under normal conditions may appear when ionic liquids are confined to a nanometer scale. As was observed in the experiment, an anomalous phase behavior from liquid to high melting point perfect crystal occurred when 1-n-butyl-3-methylimidazolium hexafluorophosphate ([bmim][PF6]) ionic liquid was confined in a carbon nanotube. In this work, we performed molecular dynamics (MD) simulations for [bmim][PF6] ionic liquid and provided direct structural evidence that the ionic crystallizes in a carbon nanotube. The ordered ionic arrangement in both the radial and the axial directions can be observed inside the channels of the CNTs to induce the form of crystallites. The ionic stacking and distributing can be determined by the sizes of the CNTs. Hydrogen bonds remain the dominant interactions between cations and anions when the ionic liquid enters into the CNT from the bulk phase. The free energies as the thermal driven forces were calculated, and it is found that it is very difficult for a single anion to enter into the channel of the CNT spontaneously. A more favorable way is through an ion-pair in which a cation “pulls” an anion to enter into the channel of the CNT together. It is predicted that other ionic liquids that possess similar structures, even including the pyridinium-based ionic liquids, can show higher melting points when confined in CNTs.
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37.
  • Egorov, Andrei V., et al. (author)
  • Molecular Dynamics Simulation Study of Glycerol-Water Liquid Mixtures
  • 2011
  • In: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 115:49, s. 14572-14581
  • Journal article (peer-reviewed)abstract
    • 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.
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38.
  • Elías-Wolff, Federico, 1983- (author)
  • A computational approach to curvature sensing in lipid bilayers
  • 2018
  • Doctoral thesis (other academic/artistic)abstract
    • Local curvature is a key driving force for spatial organization of cellular membranes, via a phenomenon known as membrane curvature sensing, where the binding energy of membrane associated macromolecules depends on the local membrane shape. However, the microscopic mechanisms of curvature sensing are not well understood. Molecular dynamics simulations offer a powerful complement to biochemical experiments, yet their contribution to the study of curvature sensing has been limited, due in part to the lack of efficient methods, not least because of methodological difficulties in dealing with curved membranes. We develop a method based on simulated buckling, which has been previously employed to study mechanical properties of membranes. Here, we describe, validate and evaluate this method. We then apply to study curvature sensing properties of three model systems, using coarse-grained simulations. On the first system, we study lipid sorting in a three-component lipid mixture with emphasis on cardiolipin. We find that if curvature is high, curvature sensing is strong enough to drive cardiolipin molecules to negative curvature regions, outcompeting other lipids, without the need of external interactions or cooperative effects. We then simulated three systems consisting of a short amphipathic peptide attached to the surface of a buckled membrane. All three peptides localize to positive curvature, in agreement with the so-called cylindrical hydrophobic insertion mechanism. Their orientational preferences, however, defy the prediction of alignment perpendicular to the direction of maximum curvature. They also fail to show expected symmetries, indicating there is more to the picture than purely shape-based effects. The curvature sensing probe of the next system is a transmembrane trimeric protein, which shows preference to intermediate curvature, in agreement with theoretical predictions. But the lack of an expected 2-fold rotation symmetry indicates that the trimer senses the local curvature gradient, and not just the point-wise local curvature. Finally, dispensing with the buckling methodology, we simulated a series of symmetric transmembrane multimers embedded in cylindrical bilayers. Based on the results of these simulations and theoretical arguments, we discuss the relationship between structural symmetry and curvature sensitivity. We conclude that anisotropic (i.e. orientation-dependent) curvature sensing is strongly limited by odd and high order rotational symmetries. However, measurements of in-plane orientation on peptides and asymmetric proteins, as well as dimers and tetramers, should yield valuable information. Our method, along with our initial conclusions, provides an useful tool for the understanding of the relationship between membrane shape and membrane protein function, and should prove useful to biophysicists in the design and interpretation of experimental curvature sensing assays.
  •  
39.
  • Elías-Wolff, Federico, et al. (author)
  • Computing Curvature Sensitivity of Biomolecules in Membranes by Simulated Buckling
  • 2018
  • In: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 14:3, s. 1643-1655
  • Journal article (peer-reviewed)abstract
    • Membrane curvature sensing, where the binding free energies of membrane-associated molecules depend on the local membrane curvature, is a key factor to modulate and maintain the shape and organization of cell membranes. However, the microscopic mechanisms are not well understood, partly due to absence of efficient simulation methods. Here, we describe a method to compute the curvature dependence of the binding free energy of a membrane associated probe molecule that interacts with a buckled membrane, which has been created by lateral compression of a flat bilayer patch. This buckling approach samples a wide range of curvatures in a single simulation, and anisotropic effects can be extracted from the orientation statistics. We develop an efficient and robust algorithm to extract the motion of the probe along the buckled membrane surface, and evaluate its numerical properties by extensive sampling of three coarse-grained model systems: local lipid density in a curved environment for single-component bilayers, curvature preferences of individual lipids in two-component membranes, and curvature sensing by a homotrimeric transmembrane protein. The method can be used to complement experimental data from curvature partition assays and provides additional insight into mesoscopic theories and molecular mechanisms for curvature sensing.
  •  
40.
  • Elias-Wolff, Federico, et al. (author)
  • Curvature sensing by cardiolipin in simulated buckled membranes
  • 2019
  • In: Soft Matter. - : Royal Society of Chemistry (RSC). - 1744-683X .- 1744-6848. ; 15:4, s. 792-802
  • Journal article (peer-reviewed)abstract
    • Cardiolipin is a non-bilayer phospholipid with a unique dimeric structure. It localizes to negative curvature regions in bacteria and is believed to stabilize respiratory chain complexes in the highly curved mitochondrial membrane. Cardiolipin's localization mechanism remains unresolved, because important aspects such as the structural basis and strength for lipid curvature preferences are difficult to determine, partly due to the lack of efficient simulation methods. Here, we report a computational approach to study curvature preferences of cardiolipin by simulated membrane buckling and quantitative modeling. We combine coarse-grained molecular dynamics with simulated buckling to determine the curvature preferences in three-component bilayer membranes with varying concentrations of cardiolipin, and extract curvature-dependent concentrations and lipid acyl chain order parameter profiles. Cardiolipin shows a strong preference for negative curvatures, with a highly asymmetric chain order parameter profile. The concentration profiles are consistent with an elastic model for lipid curvature sensing that relates lipid segregation to local curvature via the material constants of the bilayers. These computations constitute new steps to unravel the molecular mechanism by which cardiolipin senses curvature in lipid membranes, and the method can be generalized to other lipids and membrane components as well.
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41.
  •  
42.
  • Ermilova, Inna, et al. (author)
  • Cholesterol in phospholipid bilayers : positions and orientations inside membranes with different unsaturation degrees
  • 2019
  • In: Soft Matter. - 1744-683X .- 1744-6848. ; 15:1, s. 78-93
  • Journal article (peer-reviewed)abstract
    • Cholesterol is an essential component of all animal cell membranes and plays an important role in maintaining the membrane structure and physical–chemical properties necessary for correct cell functioning. The presence of cholesterol is believed to be responsible for domain formation (lipid rafts) due to different interactions of cholesterol with saturated and unsaturated lipids. In order to get detailed atomistic insight into the behaviour of cholesterol in bilayers composed of lipids with varying degrees of unsaturation, we have carried out a series of molecular dynamics simulations of saturated and polyunsaturated lipid bilayers with different contents of cholesterol, as well as well-tempered metadynamics simulations with a single cholesterol molecule in these bilayers. From these simulations we have determined distributions of cholesterol across the bilayer, its orientational properties, free energy profiles, and specific interactions of molecular groups able to form hydrogen bonds. Both molecular dynamics and metadynamics simulations showed that the most unsaturated bilayer with 22:6 fatty acid chains shows behaviour which is most different from other lipids. In this bilayer, cholesterol is relatively often found in a “flipped” configuration with the hydroxyl group oriented towards the membrane middle plane. This bilayer has also the highest (least negative) binding free energy among liquid phase bilayers, and the lowest reorientation barrier. Furthermore, cholesterol molecules in this bilayer are often found to form head-to-tail contacts which may lead to specific clustering behaviour. Overall, our simulations support ideas that there can be a subtle interconnection between the contents of highly unsaturated fatty acids and cholesterol, deficiency or excess of each of them is related to many human afflictions and diseases.
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43.
  • Ermilova, Inna, et al. (author)
  • Extension of the Slipids Force Field to Polyunsaturated Lipids
  • 2016
  • In: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 120:50, s. 12826-12842
  • Journal article (peer-reviewed)abstract
    • 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.
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44.
  • Ermilova, Inna, 1983- (author)
  • Modeling of biomembranes: from computational toxicology to simulations of neurodegenerative diseases
  • 2019
  • Doctoral thesis (other academic/artistic)abstract
    • It was known from the middle of the last century that a cell-membrane is a lipid bilayer. Since that time a large number of experimental studies has been done in order to see how a certain molecule can penetrate through a membrane. Due to the complexity of laboratory experiments computational chemistry became a convenient tool for investigations involving this process. In a real life a compound has to pass through several membranes of different chemical composition before reaching the actual target. Such a diversity in constitution gives a various selectivity to cell-membranes: some molecules will penetrate through them and others will not. That is why the development and a choice of suitable models for lipid bilayers are important steps in such a research. In this thesis new all-atomistic models for polyunsaturated phospholipids in cis conformations have been derived and added to the SLipids force field. After a successful force field validation, the new lipid models were used in molecular dynamics and well-tempered metadynamics simulations of several problems, such as toxicity of hydroxylated polybrominated diphenyl ethers (OH-PBDE), behavior of cholesterol in various membranes, an aggregation of amyloid-β (Aβ) peptides. The significance of the presence of lipid unsaturation has been demonstrated by all computations. 2’-OH-BDE68 (ortho) showed the affinity to saturated lipid bilayer, but had more conformational variations in the center of the unsaturated membrane. Cholesterol did not exhibit the preference to polynsaturated lipid bilayers from free energy calculations, but the diversity in orientations of this molecule, depending on its locations was observed. The behavior of Aβ peptides was dependent on membrane saturation as well. The insertion of Aβ peptides was detected in lipid bilayers containing higher amounts of polyunsaturated phospholipids, while in systems with more saturated membranes amyloids aggregated on membrane surfaces. Moreover, a comparison of simulations for quadro- and mono-component lipid bilayers showed that the membrane built of 18:0-22:6 PC can serve as a good model for the ’healthy’ tissue of a human brain. Also the lipid bilayer built of 14:0-14:0 PC exhibited similar features as the quadro-lipid membrane representing the brain tissue affected by Alzheimer’s disease. Good agreement of some computational results with available experimental findings demonstrated the applicability of computer simulations to real life problems.
  •  
45.
  • Ermilova, Inna, 1983-, et al. (author)
  • Modelling of interactions between Aβ(25-35) peptide and phospholipid bilayers : effects of cholesterol and lipid saturation
  • 2020
  • In: RSC Advances. - : Royal Society of Chemistry (RSC). - 2046-2069. ; 10:7, s. 3902-3915
  • Journal article (peer-reviewed)abstract
    • Aggregation of amyloid beta (Aβ) peptides in neuronal membranes is a known promoter of Alzheimer’s disease. To gain insight into the molecular details of Aβ peptide aggregation and its effect on model neuronal membranes, we carried out molecular dynamics simulations of the Aβ(25–35) fragment of the amyloid precursor protein in phospholipid bilayers composed of either fully saturated or highly unsaturated lipids, in the presence or absence of cholesterol. It was found that the peptide does not penetrate through any of the considered membranes, but can reside in the headgroup region and upper part of the lipid tails showing a clear preference to a polyunsaturated cholesterol-free membrane. Due to the ordering and condensing effect upon addition of cholesterol, membranes become more rigid facilitating peptide aggregation on the surface. Except for the case of the cholesterol-free saturated lipid bilayer, the peptides have a small effect on the membrane structure and ordering. It was also found that the most “active” amino-acid for peptide–lipid and peptide–cholesterol interaction is methionine-35, followed by asparagine-27 and serine-26, which form hydrogen bonds between peptides and polar atoms of lipid headgroups. These amino acids are also primarily responsible for peptide aggregation. This work will be relevant for designing strategies to develop drugs to combat Alzheimer’s disease.
  •  
46.
  • Ermilova, Inna, et al. (author)
  • Quantum chemical and molecular dynamics modelling of hydroxylated polybrominated diphenyl ethers
  • 2017
  • In: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 19:41, s. 28263-28274
  • Journal article (peer-reviewed)abstract
    • A series of 19 hydroxylated polybrominated diphenyl ethers (OH-PBDEs) have been studied using density functional theory (DFT) and molecular dynamics simulations with the purpose of investigating eventual correlations between their physicochemical properties and toxic action. Dissociation constants (pK(a)), solvation free energies and octanol-water partition coefficients (logP) have been computed. Additionally, metadynamics simulations of OH-PBDEs passing through a lipid bilayer have been carried out for four OH-PBDE species. No correlations between computed pKa values and toxicity data have been found. Medium correlations were found between partition coefficients and the ability of OH-PBDEs to alter membrane potential in cell cultures, which is attributed to higher uptake of molecules with larger log P parameters. It was also demonstrated that in lipid bilayers, OH-PBDE molecules differ in their orientational distributions and can adopt different conformations which can affect the uptake of these molecules and influence the pathways of their toxic action.
  •  
47.
  • Fan, Yanping, et al. (author)
  • An Advanced Coarse-Grained Nucleosome Core Particle Model for Computer Simulations of Nucleosome-Nucleosome Interactions under Varying Ionic Conditions
  • 2013
  • In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:2
  • Journal article (peer-reviewed)abstract
    • In the eukaryotic cell nucleus, DNA exists as chromatin, a compact but dynamic complex with histone proteins. The first level of DNA organization is the linear array of nucleosome core particles (NCPs). The NCP is a well-defined complex of 147 bp DNA with an octamer of histones. Interactions between NCPs are of paramount importance for higher levels of chromatin compaction. The polyelectrolyte nature of the NCP implies that nucleosome-nucleosome interactions must exhibit a great influence from both the ionic environment as well as the positively charged and highly flexible N-terminal histone tails, protruding out from the NCP. The large size of the system precludes a modelling analysis of chromatin at an all-atom level and calls for coarse-grained approximations. Here, a model of the NCP that include the globular histone core and the flexible histone tails described by one particle per each amino acid and taking into account their net charge is proposed. DNA wrapped around the histone core was approximated at the level of two base pairs represented by one bead (bases and sugar) plus four beads of charged phosphate groups. Computer simulations, using a Langevin thermostat, in a dielectric continuum with explicit monovalent (K+), divalent (Mg2+) or trivalent (Co(NH3)(6)(3+)) cations were performed for systems with one or ten NCPs. Increase of the counterion charge results in a switch from repulsive NCP-NCP interaction in the presence of K+, to partial aggregation with Mg2+ and to strong mutual attraction of all 10 NCPs in the presence of CoHex(3+). The new model reproduced experimental results and the structure of the NCP-NCP contacts is in agreement with available data. Cation screening, ion-ion correlations and tail bridging contribute to the NCP-NCP attraction and the new NCP model accounts for these interactions.
  •  
48.
  • Faure, B., et al. (author)
  • 2D to 3D crossover of the magnetic properties in ordered arrays of iron oxide nanocrystals
  • 2013
  • In: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 5:3, s. 953-960
  • Journal article (peer-reviewed)abstract
    • The magnetic 2D to 3D crossover behavior of well-ordered arrays of monodomain γ-Fe2O3 spherical nanoparticles with different thicknesses has been investigated by magnetometry and Monte Carlo (MC) simulations. Using the structural information of the arrays obtained from grazing incidence small-angle X-ray scattering and scanning electron microscopy together with the experimentally determined values for the saturation magnetization and magnetic anisotropy of the nanoparticles, we show that MC simulations can reproduce the thickness-dependent magnetic behavior. The magnetic dipolar particle interactions induce a ferromagnetic coupling that increases in strength with decreasing thickness of the array. The 2D to 3D transition in the magnetic properties is mainly driven by a change in the orientation of the magnetic vortex states with increasing thickness, becoming more isotropic as the thickness of the array increases. Magnetic anisotropy prevents long-range ferromagnetic order from being established at low temperature and the nanoparticle magnetic moments instead freeze along directions defined by the distribution of easy magnetization directions.
  •  
49.
  • Grote, Fredrik, et al. (author)
  • Molecular Dynamics Simulations of Furfural and 5-Hydroxymethylfurfural at Ambient and Hydrothermal Conditions
  • 2018
  • In: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 122:35, s. 8416-8428
  • Journal article (peer-reviewed)abstract
    • 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.
  •  
50.
  • Grote, Fredrik, et al. (author)
  • Optimization of Slipids Force Field Parameters Describing Headgroups of Phospholipids
  • 2020
  • In: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 124:40, s. 8784-8793
  • Journal article (peer-reviewed)abstract
    • The molecular mechanics force field Slipids developed in a series of works by Jambeck and Lyubartsev (J. Phys. Chem. B 2012, 116, 3164-3179; J. Chem. Theory Comput. 2012, 8, 2938-2948) generally provides a good description of various lipid bilayer systems. However, it was also found that order parameters of C-H bonds in the glycerol moiety of the phosphatidylcholine headgroup deviate significantly from NMR results. In this work, the dihedral force field parameters have been reparameterized in order to improve the agreement with experiment. For this purpose, we have computed energies for a large amount of lipid headgroup conformations using density functional theory on the B3P86/cc-pvqz level and optimized dihedral angle parameters simultaneously to provide the best fit to the quantum chemical energies. The new parameter set was validated for three lipid bilayer systems against a number of experimental properties including order parameters, area per lipid, scattering form factors, bilayer thickness, area compressibility and lateral diffusion coefficients. In addition, the order parameter dependence on cholesterol content in the POPC bilayer was investigated. It is shown that the new force field significantly improves agreement with the experimental order parameters for the lipid headgroup while keeping good agreement with other experimentally measured properties.
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