Enhanced sampling techniques in biomolecular simulations

Vojtech Spiwok, Zoran Sucur, Petr Hosek

Department of Biochemistry and Microbiology, University of Chemistry and Technology, Prague, Technická 3, Prague 6 166 28, Czech Republic.

Abstract

Biomolecular simulations are routinely used in biochemistry and molecular biology research; however, they often fail to match expectations of their impact on pharmaceutical and biotech industry. This is caused by the fact that a vast amount of computer time is required to simulate short episodes from the life of biomolecules. Several approaches have been developed to overcome this obstacle, including application of massively parallel and special purpose computers or non-conventional hardware. Methodological approaches are represented by coarse-grained models and enhanced sampling techniques. These techniques can show how the studied system behaves in long time-scales on the basis of relatively short simulations. This review presents an overview of new simulation approaches, the theory behind enhanced sampling methods and success stories of their applications with a direct impact on biotechnology or drug design.

Keywords: Molecular dynamics simulation; Alchemistic simulations; Parallel tempering; Metadynamics; Free energy surface; Drug design.