Enhanced Sampling Methods for Molecular Dynamics Simulations [Article v1.0]

Abstract

Enhanced sampling algorithms have emerged as powerful methods to extend the utility of molecular dynamics simulations and allow the sampling of larger portions of the configuration space of complex systems in a given amount of simulation time. This review aims to present the unifying principles of and differences between many of the computational methods currently used for enhanced sampling in molecular simulations of biomolecules, soft matter and molecular crystals. In fact, despite the apparent abundance and divergence of such methods, the principles at their core can be boiled down to a relatively limited number of statistical and physical concepts. To enable comparisons, the various methods are introduced using similar terminology and notation. We then illustrate in which ways many different methods combine features of a relatively small number of the same enhanced sampling concepts. This review is intended for scientists with an understanding of the basics of molecular dynamics simulations and statistical physics who want a deeper understanding of the ideas that underlie various enhanced sampling methods and the relationships between them. This living review is intended to be updated to continue to reflect the wealth of sampling methods as they continue to emerge in the literature.