Dynamics of proteins and biomolecular complexes: Inferring functional motions from structure

A model referred to as a Gaussian network model (GNM) was recently introduced for estimating the dynamic characteristics of biomolecular structures, based on atomic coordinates in the native conformation. The model relies on the construction of a Kirchhoff matrix of contacts between sufficiently close interaction sites, the latter being conveniently chosen as the individual residues of the protein, or nucleotides of the nucleic acid. Knowledge of Kirchhoff matrix permits us to determine the fluctuation behavior in the neighborhood of the folded structure, a modal decomposition of which yields information on the cooperative modes of motion. Application of the GNM to several systems is presented. The model accurately predicts the X-ray crystallographic temperature factors and the Gibbs free energy changes associated with H/D exchange in solution near native state conditions. The utility of the GNM and related mode decomposition method for extracting information on the structural elements cooperatively involved in biological function is illustrated by application to an intact imunoglobulin G structure. Regions acting as hinges and the most flexible regions involved in antigen recognition are accurately identified, in close agreement with experimental observations.