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Protein-ligand (un)binding simulations are a recent focus of biased molecular dynamics simulations. Such binding and unbinding can occur via different pathways in and out of a binding site. We here present a theoretical framework how to…

Soft Condensed Matter · Physics 2023-03-27 Steffen Wolf , Matthias Post , Gerhard Stock

Large parallel gains in the development of both computational resources as well as sampling methods have now made it possible to simulate dissociation events in ligand-protein complexes with all--atom resolution. Such encouraging progress,…

Molecular dynamics simulations use statistical mechanics at the atomistic scale to enable both the elucidation of fundamental mechanisms and the engineering of matter for desired tasks. The behavior of molecular systems at the microscale is…

Computational Physics · Physics 2020-12-25 Wujie Wang , Simon Axelrod , Rafael Gómez-Bombarelli

Due to the contribution of drug-target binding kinetics to drug efficacy, there is a high level of interest in developing methods to predict drug-target binding kinetic parameters. During the review period, a wide range of enhanced sampling…

Quantitative Methods · Quantitative Biology 2020-08-10 Ariane Nunes-Alves , Daria B. Kokh , Rebecca C. Wade

We here report on non-equilibrium targeted Molecular Dynamics simulations as tool for the estimation of protein-ligand unbinding kinetics. Correlating simulations with experimental data from SPR kinetics measurements and X-ray…

In order to inquire the microscopic origin of observed multiple time scales in solvation dynamics we carry out several computer experiments. We perform atomistic molecular dynamics simulations on three protein-water systems namely,…

Soft Condensed Matter · Physics 2017-10-18 Sayantan Mondal , Saumyak Mukherjee , Biman Bagchi

A key factor influencing a drug's efficacy is its residence time in the binding pocket of the host protein. Using atomistic computer simulation to predict this residence time and the associated dissociation process is a desirable but…

Soft Condensed Matter · Physics 2015-10-08 Pratyush Tiwary , Jagannath Mondal , Joseph A. Morrone , B. J. Berne

Accelerated molecular dynamics (MD) simulations are implemented to model the sliding process of AFM experiments at speeds close to those found in experiment. In this study the hyperdynamics method, originally devised to extend MD time…

Materials Science · Physics 2015-05-14 Woo Kyun Kim , Michael L. Falk

Non-equilibrium molecular dynamics simulations, of crucial importance in sliding friction, are hampered by arbitrariness and uncertainties in the way Joule heat is removed. We implement in a realistic frictional simulation a parameter-free,…

Mesoscale and Nanoscale Physics · Physics 2015-05-19 Andrea Benassi , Andrea Vanossi , Giuseppe E. Santoro , Erio Tosatti

The internal dynamics of macro-molecular systems is characterized by widely separated time scales, ranging from fraction of ps to ns. In ordinary molecular dynamics simulations, the elementary time step dt used to integrate the equation of…

Soft Condensed Matter · Physics 2015-05-19 Pietro Faccioli

We study unbinding of multivalent cationic ligands from oppositely charged polymeric binding sites sparsely grafted on a flat neutral substrate. Our molecular dynamics (MD) simulations are suggested by single-molecule studies of protein-DNA…

Biological Physics · Physics 2018-02-21 Aykut Erbas , Monica Olvera de la Cruz , John F. Marko

In multi-resolution simulations, different system components are simultaneously modelled at different levels of resolution, these being smoothly coupled together. In the case of enzyme systems, computationally expensive atomistic detail is…

Biological Physics · Physics 2016-11-03 Aoife C. Fogarty , Raffaello Potestio , Kurt Kremer

The dissociation of ligands from proteins and other biomacromolecules occurs over a wide range of timescales. For most pharmaceutically relevant inhibitors, these timescales are far beyond those that are accessible by conventional molecular…

Biomolecules · Quantitative Biology 2020-10-13 Daria B. Kokha , Bernd Doser , Stefan Richter , Fabian Ormersbach , Xingyi Cheng , Rebecca C. Wade

The unbinding process of a protein-ligand complex of major biological interest was investigated by means of a computational approach at atomistic classical mechanical level. An energy minimisation-based technique was used to determine the…

Biological Physics · Physics 2009-11-13 Elsa S. Henriques , Andrey V. Solov'yov

Molecular dynamics study of a thin (one to five layers) lubricant film between two substrates in moving contact are performed using Langevin equations with an external damping coefficient depending on distance and velocity of atoms relative…

Materials Science · Physics 2009-10-31 O. M. Braun , M. Peyrard

Non-equilibrium molecular dynamics simulations, of crucial importance in sliding friction, are hampered by arbitrariness and uncertainties in the removal of the frictionally generated Joule heat. Building upon general pre-existing…

Materials Science · Physics 2012-08-29 A. Benassi , A. Vanossi , G. E. Santoro , E. Tosatti

The molecular dynamics (MD) simulation study of solvation structure and free energetics in 1-ethyl-3-methylimidazolium chloride and 1-ethyl-3-methylimidazolium hexafluorophosphate using a probe solute in the preceding article [Y. Shim, M.…

Soft Condensed Matter · Physics 2009-11-11 Y. Shim , M. Y. Choi , H. J. Kim

Molecular dynamics (MD) simulations are essential tools in computational chemistry and drug discovery, offering crucial insights into dynamic molecular behavior. However, their utility is significantly limited by substantial computational…

Chemical Physics · Physics 2025-09-04 Bin Feng , Jiying Zhang , Xinni Zhang , Zijing Liu , Yu Li

Studying the pathways of ligand-receptor binding is essential to understand the mechanism of target recognition by small molecules. The binding free energy and kinetics of protein-ligand complexes can be computed using molecular dynamics…

Chemical Physics · Physics 2023-08-14 Dhiman Ray , Michele Parrinello

Molecular dynamics with the stochastic process provides a convenient way to compute structural and thermodynamic properties of chemical, biological, and materials systems. It is demonstrated that the virtual dynamics case that we proposed…

Statistical Mechanics · Physics 2018-03-20 Dezhang Li , Zifei Chen , Zhijun Zhang , Jian Liu
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