Title: Signal Propagation in Proteins and Relation to Equilibrium Fluctuations

Abstract:
Elastic network models have been widely used in recent years for describing protein dynamics, based on the premise that the motions naturally accessible to native structures are relevant to biological function. From our modeling studies we learned that a major determinant of the dynamic characteristics of biomolecules is the inter-residue contact topology in the 3-d structure. Here, we postulate that the contact topology determines not only the inherent dynamic characteristics but also, the communication pathways mediating allosteric signal transmission.

To this end, we model the protein structure as a network of inter-residue interactions and investigate the ensemble properties of a Markov process based network communication. In particular, we measure hit and commute times, analogous to mean-first passage times, for sending and receiving signals between any pair of residues. Applying this new approach to five different enzymes, we demonstrate that functionally active residues possess enhanced communication propensities. Furthermore, secondary structural elements emerge as efficient mediators of communication. These findings are insightful in understanding the topological basis of communication in proteins and the design principles for efficient signal transmission.

While hit/commute times are information-theoretic concepts, a central contribution of this work is to show that they have physical origins directly relevant to the equilibrium fluctuations of residues predicted by elastic network models.