| Proteins in vivo are not completely rigid molecules, and mobilities within their structure play a key role in protein function. We discuss a novel method for measuring two distinct types of protein flexibility by comparing pairs of static protein structure coordinates. The measures focus on the mobility of a subset of atoms in the protein known as the backbone, and they quantify mobility or flexibility at the level of the amino acids (or residues), which are the basic constituents of proteins. We validate our measures against a subset of proteins from the protein-protein docking benchmark, and against a number of individual proteins known to have mobility or flexibility that is significant to their function. We also demonstrate the applicability of our methodology to several important biochemical topics including examples that apply to drug and enzyme design, and evaluation of computational protein structure prediction. We conclude with an analysis of protein structural and energetic terms showing which terms are associated with our flexibility measures, and may therefore be useful within the context of protein modeling algorithms to predict the locality of flexible regions. |
