SYSTEMATIC ANALYSIS OF MOTIONS AND COMMUNICATION NETWORKS IN A BENCHMARK SET OF ALLOSTERIC PROTEINS

ii Allosteric proteins bind an effector molecule at one site resulting in a functional change at a second site, and mechanical and chemical processes at the molecular level are a crucial part of the basis of allosteric regulation. In this thesis, I investigate the structural basis of allostery by a systematic analysis of the differences between known inactive and active structures of allosteric proteins and putative communication networks arising from these structural changes. I collect a benchmark set of 51 allosteric proteins with crystal structures in both inactive and active states, the largest such set yet assembled. First, I systematically analyze local conformational differences between inactive and active forms of the 51 proteins to reveal general principles about the extent and structural distribution of such motions. For example, allosteric proteins consistently exhibit substantial changes in the average structure involving about 20 percent of the residues, and allosteric motions are strongly biased toward weakly constrained regions such as loops and the protein surface. Second, I derive communication networks at the tertiar