Journal ArticleDOI
Long-Time-Step Molecular Dynamics through Hydrogen Mass Repartitioning.
TLDR
Since no significant difference in kinetics or thermodynamics is observed by the use of fast HMR trajectories, further evidence is provided that long-time-step HMR MD simulations are a viable tool for accelerating molecular dynamics simulations for molecules of biochemical interest.Abstract:
Previous studies have shown that the method of hydrogen mass repartitioning (HMR) is a potentially useful tool for accelerating molecular dynamics (MD) simulations. By repartitioning the mass of heavy atoms into the bonded hydrogen atoms, it is possible to slow the highest-frequency motions of the macromolecule under study, thus allowing the time step of the simulation to be increased by up to a factor of 2. In this communication, we investigate further how this mass repartitioning allows the simulation time step to be increased in a stable fashion without significantly increasing discretization error. To this end, we ran a set of simulations with different time steps and mass distributions on a three-residue peptide to get a comprehensive view of the effect of mass repartitioning and time step increase on a system whose accessible phase space is fully explored in a relatively short amount of time. We next studied a 129-residue protein, hen egg white lysozyme (HEWL), to verify that the observed behavior extends to a larger, more-realistic, system. Results for the protein include structural comparisons from MD trajectories, as well as comparisons of pKa calculations via constant-pH MD. We also calculated a potential of mean force (PMF) of a dihedral rotation for the MTS [(1-oxyl-2,2,5,5-tetramethyl-pyrroline-3-methyl)methanethiosulfonate] spin label via umbrella sampling with a set of regular MD trajectories, as well as a set of mass-repartitioned trajectories with a time step of 4 fs. Since no significant difference in kinetics or thermodynamics is observed by the use of fast HMR trajectories, further evidence is provided that long-time-step HMR MD simulations are a viable tool for accelerating MD simulations for molecules of biochemical interest.read more
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Journal ArticleDOI
Role of Molecular Dynamics and Related Methods in Drug Discovery.
TL;DR: The theoretical background of MD and enhanced sampling methods is reviewed, focusing on free-energy perturbation, metadynamics, steered MD, and other methods most consistently used to study drug-target binding.
Journal ArticleDOI
ff19SB: Amino-Acid-Specific Protein Backbone Parameters Trained against Quantum Mechanics Energy Surfaces in Solution.
Chuan Tian,Koushik Kasavajhala,Kellon A.A. Belfon,Lauren Raguette,He Huang,Angela N. Migues,John Bickel,Yuzhang Wang,Jorge Pincay,Qin Wu,Carlos Simmerling +10 more
TL;DR: The updated model presented here, ff19SB, when combined with a more accurate water model such as OPC, should have better predictive power for modeling sequence-specific behavior, protein mutations, and also rational protein design.
Journal ArticleDOI
Structure of the µ-opioid receptor–G i protein complex
Antoine Koehl,Hongli Hu,Shoji Maeda,Yan Zhang,Qianhui Qu,Joseph M. Paggi,Naomi R. Latorraca,Daniel Hilger,Roger J. P. Dawson,Hugues Matile,Gebhard F. X. Schertler,Gebhard F. X. Schertler,Sébastien Granier,William I. Weis,Ron O. Dror,Aashish Manglik,Georgios Skiniotis,Brian K. Kobilka +17 more
TL;DR: In this article, a 3.5-dimensional structure of the μ-opioid receptor (μOR) bound to the agonist peptide DAMGO and nucleotide-free Gi was determined.
Journal ArticleDOI
Refinement of the Sugar–Phosphate Backbone Torsion Beta for AMBER Force Fields Improves the Description of Z- and B-DNA
Marie Zgarbová,Jiří Šponer,Jiří Šponer,Michal Otyepka,Thomas E. Cheatham,Rodrigo Galindo-Murillo,Petr Jurečka +6 more
TL;DR: A refinement of this potential, β(OL1), which was derived using the recently introduced methodology that includes conformation-dependent solvation effects, significantly increases the stability of the dominant ZI backbone substate and improves the overall description of the Z-DNA backbone.
Journal ArticleDOI
Assessing the Current State of Amber Force Field Modifications for DNA
Rodrigo Galindo-Murillo,James C. Robertson,Marie Zgarbová,Jiří Šponer,Jiří Šponer,Michal Otyepka,Petr Jurečka,Thomas E. Cheatham +7 more
TL;DR: A direct comparison of two of the most recent and state-of-the-art Amber force field modifications, bsc1 and OL15, that focus on accurate modeling of double-stranded DNA, concludes that both modifications are a remarkable improvement over the previous bsc0 force field.
References
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Journal ArticleDOI
Comparison of simple potential functions for simulating liquid water
TL;DR: In this article, the authors compared the Bernal Fowler (BF), SPC, ST2, TIPS2, TIP3P, and TIP4P potential functions for liquid water in the NPT ensemble at 25°C and 1 atm.
Journal ArticleDOI
Numerical Integration of the Cartesian Equations of Motion of a System with Constraints: Molecular Dynamics of n-Alkanes
TL;DR: In this paper, a numerical algorithm integrating the 3N Cartesian equations of motion of a system of N points subject to holonomic constraints is formulated, and the relations of constraint remain perfectly fulfilled at each step of the trajectory despite the approximate character of numerical integration.
Journal ArticleDOI
GROMACS 4: Algorithms for highly efficient, load-balanced, and scalable molecular simulation
TL;DR: A new implementation of the molecular simulation toolkit GROMACS is presented which now both achieves extremely high performance on single processors from algorithmic optimizations and hand-coded routines and simultaneously scales very well on parallel machines.
Journal ArticleDOI
Development and testing of a general amber force field.
TL;DR: A general Amber force field for organic molecules is described, designed to be compatible with existing Amber force fields for proteins and nucleic acids, and has parameters for most organic and pharmaceutical molecules that are composed of H, C, N, O, S, P, and halogens.
Journal ArticleDOI
A Second Generation Force Field for the Simulation of Proteins, Nucleic Acids, and Organic Molecules
Wendy D. Cornell,Piotr Cieplak,Piotr Cieplak,Christopher I. Bayly,Christopher I. Bayly,Ian R. Gould,Ian R. Gould,Kenneth M. Merz,Kenneth M. Merz,David M. Ferguson,David M. Ferguson,David C. Spellmeyer,David C. Spellmeyer,Thomas R. Fox,James W. Caldwell,Peter A. Kollman +15 more
TL;DR: Weiner et al. as mentioned in this paper derived a new molecular mechanical force field for simulating the structures, conformational energies, and interaction energies of proteins, nucleic acids, and many related organic molecules in condensed phases.