Mapping Allosteric Communication Pathways in Protein Conformational Ensembles

Abstract:

Detailed understanding of how conformational dynamics orchestrates function in allosteric regulation of recognition and catalysis at atomic resolution remains ambiguous. The three dimensional structure of protein is not always adequate to provide a complete understanding of protein function. We use atomistic molecular dynamics simulations to complement experiments to understand how protein conformational dynamics are coupled to allosteric function. We analyze multi-dimensional simulation trajectories by mapping key dynamical features within individual macrostates as residue-residue contacts.

In this talk, we will discuss computational studies and evolutionary analysis of members of a ubiquitous family of enzymes that regulate many sub-cellular processes. The effects of distal mutations and substrate binding are observed at locations far beyond the mutation and binding sites, implying their importance in allostery. The results provide insights into the general interplay between enzyme conformational dynamics and catalysis from an atomistic perspective that have implications for structure-based drug design and protein engineering.