From Distinct to Differential Conformational Dynamics to Map Allosteric Communication Pathways in Proteins.

Initiation of biological processes involving protein-ligand binding, transient protein-protein interactions, or amino acid modifications alters the conformational dynamics of proteins. Accompanying these biological processes are ensuing coupled atomic level conformational changes within the proteins. These conformational changes collectively connect multiple amino acid residues at distal allosteric, binding, and/or active sites. Local changes due to, for example, binding of a regulatory ligand at an allosteric site initiate the allosteric regulation. The allosteric signal propagates throughout the protein structure, causing changes at distal sites, activating, deactivating, or modifying the function of the protein. Hence, dynamical responses within protein structures to stimuli contain critical information on protein function. In this Perspective, we examine the description of allosteric regulation from protein dynamical responses and associated alternative and emerging computational approaches to map allosteric communication pathways between distal sites in proteins at the atomic level.