Molecular Dynamics Simulations

Abstract

Molecular dynamics has evolved from a niche method mainly applicable to model systems into a cornerstone in molecular biology. It provides us with a powerful toolbox that enables us to follow and understand structure and dynamics with extreme detail—literally on scales where individual atoms can be tracked. However, with great power comes great responsibility: Simulations will not magically provide valid results, but it requires a skilled researcher. This chapter introduces you to this, and makes you aware of some potential pitfalls. We focus on the two basic and most used methods; optimizing a structure with energy minimization and simulating motion with molecular dynamics. The statistical mechanics theory is covered briefly as well as limitations, for instance the lack of quantum effects and short timescales. As a practical example, we show each step of a simulation of a small protein, including examples of hardware and software, how to obtain a starting structure, immersing it in water, and choosing good simulation parameters. You will learn how to analyze simulations in terms of structure, fluctuations, geometrical features, and how to create ray-traced movies for presentations. With modern GPU acceleration, a desktop can perform μs-scale simulations of small proteins in a day—only 15 years ago this took months on the largest supercomputer in the world. As a final exercise, we show you how to set up, perform, and interpret such a folding simulation.