scholarly journals A new lipid force field (FUJI)

2018 ◽  
Author(s):  
Nozomu Kamiya ◽  
Keiko Shinoda ◽  
Hideaki Fujitani
Keyword(s):  
Force Field ◽  
Lipid Bilayers ◽  
Lateral Diffusion ◽  
Multidrug Efflux ◽  
Amber Force Field ◽  
Torsion Energy ◽  
Area Per Lipid ◽  
The Stability ◽  
Dynamics Simulations ◽  
High Level

AbstractTo explore inhomogeneous and anisotropic systems such as lipid bilayers, the Lennard-Jones particle mesh Ewald (LJ-PME) method was applied without a traditional isotropic dispersion correction. As the popular AMBER and CHARMM lipid force fields were developed using a cutoff scheme, their lipid bilayers unacceptably shrank when using LJ-PME method. A new lipid force field (FUJI) was developed on the basis of the AMBER force field scheme including the Lipid14 van der Waals parameters. Point charges were calculated by the restrained electrostatic potentials of many lipid conformers. The torsion energy profiles were calculated by high level ab initio molecular orbitals (LCCSD(T)/Aug-cc-pVTZ//LMP2/Aug-cc-pVTZ); then, the molecular mechanical dihedral parameters were derived by means of a fast Fourier transform. Incorporating these parameters into a new lipid force field without any fittings to experimental data, desirable lipid characteristics such as the area per lipid and lateral diffusion coefficients were obtained by GROMACS molecular dynamics simulations using the LJ-PME method and hydrogen virtual sites. The stability and structures of large membranes with undulatory fluctuations were studied by a multidrug efflux transporter (AcrABZ-TolC) with inner and outer membranes.

scholarly journals Molecular Dynamics Simulations of CO2Molecules in ZIF-11 Using Refined AMBER Force Field

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
W. Wongsinlatam ◽  
T. Remsungnen
Keyword(s):  
Molecular Dynamics ◽  
Force Field ◽  
Molecular Dynamics Simulations ◽  
Distribution Functions ◽  
Binding Energies ◽  
Hydrogen Atoms ◽  
Amber Force Field ◽  
Bonding Parameters ◽  
Flexible Framework ◽  
Dynamics Simulations

Nonbonding parameters of AMBER force field have been refined based onab initiobinding energies of CO2–[C7H5N2]−complexes. The energy and geometry scaling factors are obtained to be 1.2 and 0.9 forεandσparameters, respectively. Molecular dynamics simulations of CO2molecules in rigid framework ZIF-11, have then been performed using original AMBER parameters (SIM I) and refined parameters (SIM II), respectively. The site-site radial distribution functions and the molecular distribution plots simulations indicate that all hydrogen atoms are favored binding site of CO2molecules. One slight but notable difference is that CO2molecules are mostly located around and closer to hydrogen atom of imidazolate ring in SIM II than those found in SIM I. The Zn-Zn and Zn-N RDFs in free flexible framework simulation (SIM III) show validity of adapting AMBER bonding parameters. Due to the limitations of computing resources and times in this study, the results of flexible framework simulation using refined nonbonding AMBER parameters (SIM IV) are not much different from those obtained in SIM II.

scholarly journals Data for molecular dynamics simulations of B-type cytochrome c oxidase with the Amber force field

Data in Brief ◽  
2016 ◽  
Vol 8 ◽  
pp. 1209-1214 ◽  
Author(s):  
Longhua Yang ◽  
Åge A. Skjevik ◽  
Wen-Ge Han Du ◽  
Louis Noodleman ◽  
Ross C. Walker ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Cytochrome C ◽  
Force Field ◽  
Molecular Dynamics Simulations ◽  
Cytochrome C Oxidase ◽  
Amber Force Field ◽  
Dynamics Simulations

scholarly journals Interactions of the designed antimicrobial peptide MB21 and truncated dermaseptin S3 with lipid bilayers: molecular-dynamics simulations

2003 ◽  
Vol 370 (1) ◽  
pp. 233-243 ◽  
Author(s):  
Craig M. SHEPHERD ◽  
Hans J. VOGEL ◽  
D. Peter TIELEMAN
Keyword(s):  
Molecular Dynamics ◽  
Antimicrobial Peptide ◽  
Molecular Dynamics Simulations ◽  
Lipid Bilayers ◽  
Helical Conformation ◽  
Constraint Forces ◽  
Surface Binding ◽  
Lipid Interactions ◽  
Area Per Lipid ◽  
Dynamics Simulations

Molecular-dynamics simulations covering 30ns of both a natural and a synthetic antimicrobial peptide in the presence of a zwitterionic lipid bilayer were performed. In both simulations, copies of the peptides were placed in an α-helical conformation on either side of the bilayer about 10Å (1Å = 0.1nm) from the interface, with either the hydrophobic or the positively charged face of the helix directed toward the bilayer surface. The degree of peptide—lipid interaction was dependent on the starting configuration: surface binding and subsequent penetration of the bilayer was observed for the hydrophobically oriented peptides, while the charge-oriented peptides demonstrated at most partial surface binding. Aromatic residues near the N-termini of the peptides appear to play an important role in driving peptide—lipid interactions. A correlation between the extent of peptide—lipid interactions and helical stability was observed in the simulations. Insertion of the peptides into the bilayer caused a dramatic increase in the lateral area per lipid and decrease in the bilayer thickness, resulting in substantial disordering of the lipid chains. Results from the simulations are consistent with early stages of proposed mechanisms for the lytic activity of antimicrobial peptides. In addition to these ‘free’ simulations, 25ns simulations were carried out with the peptides constrained at three different distances relative to the bilayer interface. The constraint forces are in agreement with the extent of peptide—bilayer insertion observed in the free simulations.

scholarly journals W-RESP: Well-Restrained Electrostatic Potential Derived Charges. Revisiting the Charge Derivation Model

2020 ◽  
Author(s):  
Michal Janeček ◽  
Petra Kührová ◽  
Vojtěch Mlýnský ◽  
Michal Otyepka ◽  
Jiří Šponer ◽  
...  
Keyword(s):  
Force Field ◽  
Electrostatic Potential ◽  
Electrostatic Interactions ◽  
Force Fields ◽  
Amber Force Field ◽  
Heterocyclic Molecules ◽  
Partial Charges ◽  
Grid Points ◽  
Dynamics Simulations ◽  
Extra Point

ABSTRACTRepresentation of electrostatic interactions by a Coulombic pair-wise potential between atom-centered partial charges is a fundamental and crucial part of empirical force fields used in classical molecular dynamics simulations. The broad success of the AMBER force field family originates mainly from the restrained electrostatic potential (RESP) charge model, which derives partial charges to reproduce the electrostatic field around the molecules. However, description of the electrostatic potential around molecules by standard RESP may be biased for some types of molecules. In this study, we modified the RESP charge derivation model to improve its description of the electrostatic potential around molecules, and thus electrostatic interactions in the force field. In particular, we re-optimized the atomic radii for definition of the grid points around the molecule, redesigned the restraining scheme and included extra point charges. The RESP fitting was significantly improved for aromatic heterocyclic molecules. Thus, the suggested W-RESP(-EP) charge derivation model showed clear potential for improving the performance of the nucleic acid force fields, for which poor description of nonbonded interactions, such as underestimated base pairing, makes it difficult to describe the folding free energy landscape of small oligonucleotides.

scholarly journals Development of OPLS-AA/M Parameters for Simulations of G Protein-Coupled Receptors and Other Membrane Proteins

2022 ◽  
Author(s):  
Michael J. Robertson ◽  
Georgios Skiniotis
Keyword(s):  
Membrane Proteins ◽  
Force Field ◽  
G Protein ◽  
Drug Targets ◽  
G Protein Coupled Receptors ◽  
Dynamic Nature ◽  
Post Translational Modifications ◽  
Dynamics Simulations ◽  
High Level ◽  
G Protein Coupled

G protein-coupled receptors (GPCRs) and other membrane proteins are valuable drug targets, and their dynamic nature makes them attractive systems for study with molecular dynamics simulations and free energy approaches. Here, we report the development, implementation, and validation of OPLS-AA/M force field parameters to enable simulations of these systems. These efforts include the introduction of post-translational modifications including lipidations and phosphorylation. We also modify previously reported parameters for lipids to be more consistent with the OPLS-AA force field standard and extend their coverage. These new parameters are validated on a variety of test systems, with the results compared to high-level quantum mechanics calculations, experimental data, and simulations with CHARMM36m where relevant. The results demonstrate that the new parameters reliably reproduce the behavior of membrane protein systems.

scholarly journals How well do force fields capture the strength of salt bridges in proteins?

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4967 ◽  
Author(s):  
Mustapha Carab Ahmed ◽  
Elena Papaleo ◽  
Kresten Lindorff-Larsen
Keyword(s):  
Molecular Dynamics ◽  
Force Field ◽  
Force Fields ◽  
Salt Bridge ◽  
Dynamics Simulation ◽  
Ionic Interactions ◽  
Salt Bridges ◽  
Important Interaction ◽  
The Stability ◽  
Dynamics Simulations

Salt bridges form between pairs of ionisable residues in close proximity and are important interactions in proteins. While salt bridges are known to be important both for protein stability, recognition and regulation, we still do not have fully accurate predictive models to assess the energetic contributions of salt bridges. Molecular dynamics simulation is one technique that may be used study the complex relationship between structure, solvation and energetics of salt bridges, but the accuracy of such simulations depends on the force field used. We have used NMR data on the B1 domain of protein G (GB1) to benchmark molecular dynamics simulations. Using enhanced sampling simulations, we calculated the free energy of forming a salt bridge for three possible lysine-carboxylate ionic interactions in GB1. The NMR experiments showed that these interactions are either not formed, or only very weakly formed, in solution. In contrast, we show that the stability of the salt bridges is overestimated, to different extents, in simulations of GB1 using seven out of eight commonly used combinations of fixed charge force fields and water models. We also find that the Amber ff15ipq force field gives rise to weaker salt bridges in good agreement with the NMR experiments. We conclude that many force fields appear to overstabilize these ionic interactions, and that further work may be needed to refine our ability to model quantitatively the stability of salt bridges through simulations. We also suggest that comparisons between NMR experiments and simulations will play a crucial role in furthering our understanding of this important interaction.

scholarly journals Semi-Automated Optimization of the CHARMM36 Lipid Force Field to Include Explicit Treatment of Long-Range Dispersion

2020 ◽  
Author(s):  
Yalun Yu ◽  
Andreas Kramer ◽  
Andrew Simmonett ◽  
Rick Venable ◽  
Alex MacKerell ◽  
...  
Keyword(s):  
Force Field ◽  
Lipid Bilayers ◽  
Long Range ◽  
Liquid Crystalline ◽  
Pair Correlation ◽  
Optimization Method ◽  
Free Energy Calculations ◽  
Fine Tuning ◽  
Compression Isotherm ◽  
High Level

The development of the CHARMM lipid force field (FF) can be traced back to the early 1990s with its current version denoted CHARMM36 (C36). The parametrization of C36 utilized high-level quantum mechanical data and free energy calculations of model compounds before parameters were manually adjusted to yield agreement with experimental properties of lipid bilayers. While such manual fine-tuning of FF parameters is based on intuition and trial-and-error, automated methods can identify beneficial modifications of the parameters via their sensitivities and thereby guide the optimization process. This paper introduces a semi-automated approach to reparametrize the CHARMM lipid FF with consistent inclusion of long-range dispersion through the LennardJones particle-mesh Ewald (LJ-PME) approach. The optimization method is based on thermodynamic reweighting with regularization with respect to the C36 set. Two independent optimizations with different topology restrictions are presented. Targets of the optimizations are primarily liquid crystalline phase properties of lipid bilayers and the compression isotherm of monolayers. Pair correlation functions between water and lipid functional groups in aqueous solution are also included to address headgroup hydration. While the physics of the reweighting strategy itself is well understood, applying it to heterogeneous, complex anisotropic systems poses additional challenges. These were overcome through careful selection of target properties and reweighting settings allowing for the successful incorporation of the explicit treatment of long-range dispersion, and we denote the newly optimized lipid force field as C36/LJ-PME. The current implementation of the optimization protocol will facilitate the future development of the CHARMM and related lipid force fields.<br>

Modelling the Hydrolysis of Iron-Sulfur Clusters

2019 ◽  
Author(s):  
Murilo H. Teixeira ◽  
Felipe Curtolo ◽  
Sofia R. G. Camilo ◽  
Martin J. Field ◽  
Peng Zheng ◽  
...  
Keyword(s):  
Aqueous Solution ◽  
Density Functional ◽  
Catalytic Efficiency ◽  
Implicit Solvent ◽  
Hybrid Functional ◽  
Iron Sulfur ◽  
The Stability ◽  
Dynamics Simulations ◽  
High Level ◽  
Hydrolysis Of

<div>Iron-sulfur (FeS) clusters are essential metal cofactors involved in a wide variety of biological functions. Their catalytic efficiency, biosynthesis and regulation depend on FeS stability in aqueous solution. Here, molecular modelling is used to investigate the hydrolysis of an oxidized (ferric) mononuclear FeS cluster by bare dissociation and water substitution mechanisms in neutral and acidic solution. First, approximate electronic structure descriptions of FeS reactions by density functional theory are validated against high-level wave-function CCSD(T) calculations. Solvation contributions are evaluated by an all-atom model with hybrid quantum chemical/molecular mechanical (QM/MM) potentials and enhanced sampling molecular dynamics simulations. The free energy profile obtained for FeS cluster hydrolysis indicates the hybrid functional M06 together with an implicit solvent correction capture the most important aspects of FeS cluster reactivity in aqueous solution. Then, 20 reaction channels leading to two consecutive Fe--S bond ruptures were explored with this calibrated model. For all protonation states, nucleophilic substitution with concerted bond breaking and forming to iron is the preferred mechanism, both kinetic and thermodynamically. In neutral solution, proton transfer from water to the sulfur leaving group is also concerted. Dissociative reactions show higher barriers and will not be relevant for FeS reactivity when exposed to solvent. These hydrolysis mechanisms may help to explain the stability and catalytic mechanisms of FeS clusters of multiple sizes and proteins</div><div><br></div>

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