Normal Mode Analysis Techniques in Structural Biology

The dynamic simulation of macromolecular systems with biologically relevant sizes and time scales is critical for understanding macromolecular function. In this context, normal mode analysis (NMA) approximates the complex dynamicalbehaviourofa macromoleculeas a simple setof harmonic oscillators vibrating around a given equilibrium conformation. This technique, originated from classical mechanics, was first applied to investigate the dynamical properties of small biological systems more than 30 years ago. During this time, a wealth of evidence has accumulated to support NMA as a successful tool for simulating macromolecular motions at extended length scales. Today, NMA combined with coarse-grained representations has become an efficient alternative to molecular dynamics simulations for studying the slow and largeamplitude motions of macromolecular machines. Interesting insights into these systems can be obtained very quickly with NMA to characterise their flexibility, to predict the directions of their collective conformational changes, or to help in the interpretation of experimental structural data. The recently developed methods and applications of NMA together with an introduction of the underlying theory will be briefly reviewed here. Introduction