Protein Dynamics: From Structure to Function

Abstract

Understanding protein function requires detailed knowledge about protein dynamics, i.e. the different conformational states the system can adopt. Despite substantial experimental progress, simulation techniques such as molecular dynamics (MD) currently provide the only routine means to obtain dynamical information at an atomic level on timescales of nano-to microseconds. Even with the current development of computational power, sampling techniques beyond MD are necessary to enhance conformational sampling of large proteins and assemblies thereof. The use of collective coordinates has proven to be a promising means in this respect, either as a tool for analysis or as part of new sampling algorithms. Starting from MD simulations, several enhanced sampling algorithms for biomolecular simulations are reviewed in this chapter. Examples are given throughout illustrating how consideration of the dynamic properties of a protein sheds light on its function. Molecular Dynamics SimulationsOver the last decades, experimental techniques have made substantial progress in revealing the three-dimensional structure of proteins, in particular X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy and cryo-electron microscopy. Going beyond the static picture of single protein structures has proven to be more challenging, although, a number of techniques such as NMR relaxation, fluorescence spectroscopy or time-resolved X-ray crystallography have emerged