scholarly journals Influence of cut-off truncation and artificial periodicity of electrostatic interactions in molecular simulations of solvated ions: A continuum electrostatics study

2003 ◽  
Vol 119 (17) ◽  
pp. 9129-9144 ◽  
Author(s):  
Michael Bergdorf ◽  
Christine Peter ◽  
Philippe H. Hünenberger
Keyword(s):  
Electrostatic Interactions ◽  
Molecular Simulations ◽  
Continuum Electrostatics ◽  
Solvated Ions

Characterizing the Water Wire in the Gramicidin Channel Found by Monte Carlo Sampling Using Continuum Electrostatics and in Molecular Dynamics Trajectories with Conventional or Polarizable Force Fields

2020 ◽  
pp. 1-20
Author(s):  
Yingying Zhang ◽  
Kamran Haider ◽  
Divya Kaur ◽  
Van A. Ngo ◽  
Xiuhong Cai ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Dipole Moment ◽  
Electrostatic Interactions ◽  
Hybrid Methods ◽  
Force Fields ◽  
Proton Channel ◽  
Water Molecules ◽  
Implicit Solvent ◽  
Continuum Electrostatics ◽  
Hydrogen Bond Networks

Water molecules play a key role in all biochemical processes. They help define the shape of proteins, and they are reactant or product in many reactions and are released as ligands are bound. They facilitate the transfer of protons through transmembrane proton channel, pump and transporter proteins. Continuum electrostatics (CE) force fields used by program Multiconformation CE (MCCE) capture electrostatic interactions in biomolecules with an implicit solvent, which captures the averaged solvent water equilibrium properties. Hybrid CE methods can use explicit water molecules within the protein surrounded by implicit solvent. These hybrid methods permit the study of explicit hydrogen bond networks within the protein and allow analysis of processes such as proton transfer reactions. Yet hybrid CE methods have not been rigorously tested. Here, we present an explicit treatment of water molecules in the Gramicidin A (gA) channel using MCCE and compare the resulting distributions of water molecules and key hydration features against those obtained with explicit solvent Molecular Dynamics (MD) simulations with the nonpolarizable CHARMM36 and polarizable Drude force fields. CHARMM36 leads to an aligned water wire in the channel characterized by a large absolute net water dipole moment; the MCCE and Drude analysis lead to a small net dipole moment as the water molecules change orientation within the channel. The correct orientation is not as yet known, so these calculations identify an open question.

Lattice‐sum methods for calculating electrostatic interactions in molecular simulations

1995 ◽  
Vol 103 (8) ◽  
pp. 3014-3021 ◽  
Author(s):  
Brock A. Luty ◽  
Ilario G. Tironi ◽  
Wilfred F. van Gunsteren
Keyword(s):  
Electrostatic Interactions ◽  
Molecular Simulations ◽  
Lattice Sum

scholarly journals Enhancing Sidechain Rotamer Sampling Using Non-Equilibrium Candidate Monte Carlo

2019 ◽  
Author(s):  
Kalistyn H. Burley ◽  
Samuel C. Gill ◽  
Nathan M. Lim ◽  
David Mobley
Keyword(s):  
Molecular Dynamics ◽  
Monte Carlo ◽  
Ligand Binding ◽  
Electrostatic Interactions ◽  
Molecular Simulations ◽  
Adequate Sampling ◽  
Binding Pockets ◽  
Sidechain Rotamers ◽  
Dynamics Simulations ◽  
Non Equilibrium

<div>Molecular simulations are a valuable tool for studying biomolecular motions and thermodynamics. However, such motions can be slow compared to simulation timescales, yet critical. Specifically, adequate sampling of sidechain motions in protein binding pockets proves crucial for obtaining accurate estimates of ligand binding free energies from molecular simulations. The timescale of sidechain rotamer flips can range from a few ps to several hundred ns or longer, particularly in crowded environments like the interior of proteins. Here, we apply a mixed non-equilibrium candidate Monte Carlo (NCMC)/molecular dynamics (MD) method to enhance sampling of sidechain rotamers. The NCMC portion of our method applies a switching protocol wherein the steric and electrostatic interactions between target sidechain atoms and the surrounding environment are cycled off and then back on during the course of a move proposal. Between NCMC move proposals, simulation of the system continues via traditional molecular dynamics. Here, we first validate this approach on a simple, solvated valine-alanine dipeptide system and then apply it to a well-studied model ligand binding site in T4 lysozyme L99A. We compute the rate of rotamer transitions for a valine sidechain using our approach and compare it to that of traditional molecular dynamics simulations. Here, we show that our NCMC/MD method substantially enhances sidechain sampling, especially in systems where the torsional barrier to rotation is high (>10 kcal/mol). These barriers can be intrinsic torsional barriers or steric barriers imposed by the environment.</div><div>Overall, this may provide a promising strategy to selectively improve sidechain sampling in molecular simulations.</div>

scholarly journals Enhancing Sidechain Rotamer Sampling Using Non-Equilibrium Candidate Monte Carlo

2018 ◽  
Author(s):  
Kalistyn H. Burley ◽  
Samuel C. Gill ◽  
Nathan M. Lim ◽  
David Mobley
Keyword(s):  
Molecular Dynamics ◽  
Monte Carlo ◽  
Ligand Binding ◽  
Electrostatic Interactions ◽  
Molecular Simulations ◽  
Adequate Sampling ◽  
Binding Pockets ◽  
Sidechain Rotamers ◽  
Dynamics Simulations ◽  
Non Equilibrium

<div>Molecular simulations are a valuable tool for studying biomolecular motions and thermodynamics. However, such motions can be slow compared to simulation timescales, yet critical. Specifically, adequate sampling of sidechain motions in protein binding pockets proves crucial for obtaining accurate estimates of ligand binding free energies from molecular simulations. The timescale of sidechain rotamer flips can range from a few ps to several hundred ns or longer, particularly in crowded environments like the interior of proteins. Here, we apply a mixed non-equilibrium candidate Monte Carlo (NCMC)/molecular dynamics (MD) method to enhance sampling of sidechain rotamers. The NCMC portion of our method applies a switching protocol wherein the steric and electrostatic interactions between target sidechain atoms and the surrounding environment are cycled off and then back on during the course of a move proposal. Between NCMC move proposals, simulation of the system continues via traditional molecular dynamics. Here, we first validate this approach on a simple, solvated valine-alanine dipeptide system and then apply it to a well-studied model ligand binding site in T4 lysozyme L99A. We compute the rate of rotamer transitions for a valine sidechain using our approach and compare it to that of traditional molecular dynamics simulations. Here, we show that our NCMC/MD method substantially enhances sidechain sampling, especially in systems where the torsional barrier to rotation is high (>10 kcal/mol). These barriers can be intrinsic torsional barriers or steric barriers imposed by the environment.</div><div>Overall, this may provide a promising strategy to selectively improve sidechain sampling in molecular simulations.</div>

The effect of electrostatic boundaries in molecular simulations: symmetry matters

2017 ◽  
Vol 19 (6) ◽  
pp. 4861-4876 ◽  
Author(s):  
Cong Pan ◽  
Shasha Yi ◽  
Zhonghan Hu
Keyword(s):  
Molecular Simulations ◽  
Continuum Electrostatics

Depending on the symmetry, corrections to simulated quantities might be necessary to reestablish consistency within continuum electrostatics.

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