Title: Determining residues involved in allosteric mechanisms using a volume-exclusion based algorithm

Abstract:
Low-frequency, large amplitude deformations in a protein are critical to achieving its functions. In particular, allosteric mechanisms propagate perturbations from one site of a protein to another site, often over large distances. For example, in a CREB binding protein, which regulates transcription, binding of one transcriptor factor domain influences the binding of another. To understand such a protein function, it thus becomes important to understand the allosteric mechanism. Although it is difficult to determine this mechanism accurately, several studies, experimental and computational, try to determine the residues that are most likely to play a role in it. I will present a volume-exclusion based algorithm aimed at predicting such residues. The algorithm computes a protein residue interaction graph by adapting a side-chain placement method. Initial tests on a small collection of proteins demonstrate that it determines residues involved in allosteric interactions in a way that is consistent with previous experimental methods. This algorithm could eventually serve as a useful pre-computation tool for more detailed allosteric mechanism studies, e.g., the determination of actual allosteric pathways.