The relationship between functional conformation changes and thermal dynamics of proteins is investigated with the help of the torsional network model (TNM), an elastic network model in torsion angle space that we recently introduced. We propose and test a null-model of "random" conformation changes that assumes that the contributions of normal modes to conformation changes are proportional to their contributions to thermal fluctuations. Deviations from this null model are generally small. When they are large and significant, they consist in conformation changes that are represented by very few low frequency normal modes and overcome small energy barriers. We interpret these features as the result of natural selection favoring the intrinsic protein dynamics consistent with functional conformation changes. These "selected" conformation changes are more frequently associated to ligand binding, and in particular phosphorylation, than to pairs of conformations with the same ligands. This deep relationship between the thermal dynamics of a protein, represented by its normal modes, and its functional dynamics can reconcile in a unique framework the two models of conformation changes, conformational selection and induced fit. The program TNM that computes torsional normal modes and analyzes conformation changes is available upon request. This article is part of a Special Issue entitled: The emerging dynamic view of proteins: Protein plasticity in allostery, evolution and self-assembly.
Copyright © 2012. Published by Elsevier B.V.