Enhanced Molecular Dynamics Methods Applied to Drug Design Projects

Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1762)

Abstract

Nobel Laureate Richard P. Feynman stated: “[…] everything that living things do can be understood in terms of jiggling and wiggling of atoms […].” The importance of computer simulations of macromolecules, which use classical mechanics principles to describe atom behavior, is widely acknowledged and nowadays, they are applied in many fields such as material sciences and drug discovery. With the increase of computing power, molecular dynamics simulations can be applied to understand biological mechanisms at realistic timescales. In this chapter, we share our computational experience providing a global view of two of the widely used enhanced molecular dynamics methods to study protein structure and dynamics through the description of their characteristics, limits and we provide some examples of their applications in drug design. We also discuss the appropriate choice of software and hardware. In a detailed practical procedure, we describe how to set up, run, and analyze two main molecular dynamics methods, the umbrella sampling (US) and the accelerated molecular dynamics (aMD) methods.

Key words

Conformational sampling Enhanced molecular dynamics Free energy Ligand (un)binding 

Notes

Acknowledgments

This work was supported by the Institut de Recherche Servier and the French National Research Agency (ANR-13-JSV5-0001 and ANR-15-CE20-0015). The authors wish to thank the Région Centre Val de Loire and the Ligue contre le Cancer for financial supports and the Orléans-Tours CaSciModOT at the Centre de Calcul Scientique de la Région Centre Val de Loire and the Centre Régional Informatique et d’Applications Numériques de Normandie (CRIANN) for providing computer facilities.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institut de Chimie Organique et Analytique (ICOA), UMR7311 CNRS-Université d’Orléans Université d’OrléansOrléans Cedex 2France
  2. 2.Centre de Biophysique Moléculaire (CBM), CNRS, UPR 4301Orléans Cedex 2France

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