| 1. |
- Lyubartsev, Alexander P., et al.
(författare)
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Force Field Development for Lipid Membrane Simulations
- 2016
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Ingår i: Biochimica et Biophysica Acta - Biomembranes. - : Elsevier BV. - 0005-2736 .- 1879-2642. ; 1858:10, s. 2483-2497
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Tidskriftsartikel (refereegranskat)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.
(författare)
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Recent development in computer simulations of lipid bilayers
- 2011
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Ingår i: Soft Matter. - : Royal Society of Chemistry (RSC). - 1744-683X .- 1744-6848. ; 7:1, s. 25-39
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Forskningsöversikt (refereegranskat)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.
(författare)
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Systematic coarse-graining of molecular models by the Newton inversion method
- 2010
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Ingår i: Faraday discussions. - 1359-6640 .- 1364-5498. ; 144, s. 43-56
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Tidskriftsartikel (refereegranskat)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.
(författare)
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Modeling DNA Flexibility : Comparison of Force Fields from Atomistic to Multiscale Levels
- 2020
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 124:1, s. 38-49
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Tidskriftsartikel (refereegranskat)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.
(författare)
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Effective solvent mediated potentials of Na+ and Cl− ions in aqueous solution : temperature dependence
- 2011
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Ingår i: Physical Chemistry, Chemical Physics - PCCP. - 1463-9076 .- 1463-9084. ; :13, s. 5722-5727
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Tidskriftsartikel (refereegranskat)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.
(författare)
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MagiC : Software Package for Multiscale Modeling
- 2013
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Ingår i: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 9:3, s. 1512-1520
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Tidskriftsartikel (refereegranskat)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.
(författare)
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Magic v.3 : An integrated software package for systematic structure-based coarse-graining
- 2019
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Ingår i: Computer Physics Communications. - : Elsevier BV. - 0010-4655 .- 1879-2944. ; 237, s. 263-273
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Tidskriftsartikel (refereegranskat)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-
(författare)
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Multiscale simulations of soft matter: systematic structure-based coarse-graining approach
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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.
(författare)
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Systematic Implicit Solvent Coarse Graining of Dimyristoylphosphatidylcholine Lipids
- 2014
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Ingår i: Journal of Computational Chemistry. - : Wiley. - 0192-8651 .- 1096-987X. ; 35:16, s. 1208-1218
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Tidskriftsartikel (refereegranskat)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.
(författare)
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Systematic implicit solvent coarse graining of DMPC lipids
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Tidskriftsartikel (refereegranskat)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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