Handling Electrostatic Interactions in Molecular Simulations: A Systematic Study

2008 ◽  
Vol 73 (4) ◽  
pp. 481-506 ◽  
Author(s):  
Jiří Kolafa ◽  
Filip Moučka ◽  
Ivo Nezbeda
Keyword(s):  
Molecular Dynamics ◽  
Monte Carlo ◽  
Long Range ◽  
Electrostatic Interactions ◽  
Short Range ◽  
Ewald Summation ◽  
Field Methods ◽  
Reaction Field ◽  
Lennard Jones ◽  
Dynamics Simulations

Two qualitatively different models with strong long-range electrostatic interactions, Lennard-Jones diatomics with an embedded dipole moment and TIP4P/2005 water, are considered in extensive Monte Carlo and molecular dynamics simulations to systematically study the differences in results caused by different treatments of the long-range electrostatic interactions. In addition to the standard Ewald summation and reaction field methods, we consider also two variants of short-range approximations. Both thermodynamic and structural properties, and both homogeneous and inhomogeneous phases are considered. It is shown that the accuracy of the short-range approximations with carefully selected parameters may be sufficient for a number of applications; however, in some cases one can encounter accuracy limits or structural or other artifacts.

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>

scholarly journals SARS-Cov-2 Spike binding to ACE2 is stronger and longer ranged with glycans

2021 ◽  
Author(s):  
Yihan Huang ◽  
Bradley S Harris ◽  
Shiaki A Minami ◽  
Seongwon Jung ◽  
Priya Shah ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Hydrogen Bonds ◽  
Electrostatic Interactions ◽  
Spike Protein ◽  
Binding Strength ◽  
Lennard Jones ◽  
Binding Domains ◽  
Interaction Mode ◽  
Dynamics Simulations ◽  
New Interactions

Highly detailed steered Molecular Dynamics simulations are performed on differently glycosylated receptor binding domains of the SARS-CoV-2 spike protein. The binding strength and the binding range increases with glycosylation. The interaction energy rises very quickly with pulling the proteins apart and only slowly drops at larger distances. We see a catch slip type behavior where interactions during pulling break and are taken over by new interactions forming. The dominant interaction mode are hydrogen bonds but Lennard-Jones and electrostatic interactions are relevant as well.

Sign in / Sign up

Export Citation Format

Share Document