PROTEIN ALLOSTERY: FROM BASIC MECHANISMS TO COMPUTATIONAL MODELLING

Abstract

Allostery is a phenomenon in which a protein’s functional activity is regulated by a perturbation at a distant site. Allosteric control of proteins by ligand binding, mutations, and structural disorder is explored here using a structure-based statistical mechanical model of allostery. The following findings will be presented: first, reversing allosteric communication identifies known allosteric sites and suggests latent allosteric sites; second, Allosteric Signaling Maps (ASMs), derived by exhaustive mutational scanning over all amino acids, allow to examine the allosteric effects of distal mutations quantitatively; third, allosteric regulation driven by structural disorder and order, and their transitions, will be explored in several proteins. The computationally efficient method is implemented as an online web-server called AlloSigMA2 to quantify the allosteric signaling originated from user-defined site(s) and/or mutation(s). Lastly, an online database AlloMAPS which contains the comprehensive description on allosteric signaling in more than 2,000 proteins and protein domains will be presented.