From Protein Structure to Function with Bioinformatics.pdf

Chapter 9Protein Dynamics: From Structure to FunctionMarcus B. Kubitzki, Bert L. de Groot, and Daniel SeeligerAbstract Understanding protein function requires detailed knowledge aboutprotein dynamics, i.e. the different conformational states the system can adopt.Despite substantial experimental progress, simulation techniques such as moleculardynamics (MD) currently provide the only routine means to obtain dynamicalinformation at an atomic level on timescales of nano- to microseconds. Even withthe current development of computational power, sampling techniques beyond MDare necessary to enhance conformational sampling of large proteins and assembliesthereof. The use of collective coordinates has proven to be a promising means inthis respect, either as a tool for analysis or as part of new sampling algorithms.Starting from MD simulations, several enhanced sampling algorithms for biomolecularsimulations are reviewed in this chapter. Examples are given throughoutillustrating how consideration of the dynamic properties of a protein sheds lighton its function.9.1 Molecular Dynamics SimulationsOver the last decades, experimental techniques have made substantial progress inrevealing the three-dimensional structure of proteins, in particular X-ray crystallography,nuclear magnetic resonance (NMR) spectroscopy and cryo-electronmicroscopy. Going beyond the static picture of single protein structures has provento be more challenging, although, a number of techniques such as NMR relaxation,fluorescence spectroscopy or time-resolved X-ray crystallography have emerged(Kempf and Loria 2003; Weiss 1999; Moffat 2003; Schotte et al. 2003), yieldinginformation about the inherent conformational flexibility of proteins. Despite thisenormous variety, experimental techniques having spatio-temporal resolution in theM.B. Kubitzki*, B.L. de Groot, and D. SeeligerComputational Biomolecular Dynamics Group, Max Planck Institute for Biophysical Chemistry,Am Fassberg 11, 37077, Goettingen, Germany*Corresponding author: e-mail: mkubitz@gwdg.deD.J. Rigden (ed.) From Protein Structure to Function with Bioinformatics, 217© Springer Science + Business Media B.V. 2009