37
PROTEIN MOTION: SIMULATION
“If we walk far enough,” said Dorothy, “we shall some time come to some place, I am sure.”
L. Frank Baum, in The Wonderful Wizard of Oz, 1900.
INTRODUCTION
Molecular motions of biological macromolecules underlie folding, stability, and function. Crystallographic structural snapshots (Chapter 4) as well as nuclear magnetic resonance (NMR) structural (Chapter 5) ensembles enable, with the help of bioinformatics methods, the identification of functional sites, hinge and dynamic regions, interacting partners, remote homologues, and much more valuable biophysical insights. Yet, this experimental structural view is often constrained by the lack of understanding of the underlying time-dependent mechanism bridging structure and the execution of biological function. Understanding protein motion is pivotal for deciphering functional mechanisms including folding (Daggett and Fersht, 2003; Vendruscolo and Paci, 2003; Munoz, 2007) along with the complimentary misfolding (Dobson, 2003; Chiti and Dobson, 2006; Daggett, 2006), allosteric regulation (Popovych et al., 2006; Swain and Gierasch, 2006; Gilchrist, 2007; Gu and Bourne, 2007), catalysis (Hammes-Schiffer and Benkovic, 2006), functional plasticity (Kobilka and Deupi, 2007), protein-DNA interactions (Sarai and Kono, 2005), and protein-protein interactions (Bonvin, 2006; Fernandez-Ballester and Serrano, 2006; Reichmannet al., 2007). While information from different ...
