Enhanced sampling methods for molecular dynamics simulations

TL;DR

This review explains the core principles behind various enhanced sampling methods in molecular dynamics, unifying their concepts and illustrating their relationships to improve understanding and comparison of these techniques.

Contribution

It provides a unified framework and terminology for understanding and comparing diverse enhanced sampling algorithms in molecular simulations.

Findings

Many methods are based on a limited set of core principles.

Different algorithms often combine multiple sampling concepts.

The review offers a common language for method comparison.

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 and differences of many of the computational methods currenly used for enhanced sampling in molecular simulations of biomolecules, soft matter and molecular crystals. Indeed, 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 principles. To enable comparisons, the various methods are introduced using similar terminology and notation. We then illustrate in which ways many different methods combine principles from a smaller class of 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.