Kinetic energy flows in activated dynamics of biomolecules

TL;DR

This paper develops a rigorous theoretical framework for understanding kinetic energy flows in protein conformational changes, revealing how energy transfer channels facilitate biomolecular activation processes.

Contribution

It extends previous potential energy flow models by providing a comprehensive theory for kinetic energy flows in biomolecular dynamics.

Findings

Kinetic energy flows enable energy transfer between dihedral angles during isomerization.

Theta dihedral transfers energy to phi dihedral to help cross activation barriers.

Energy transfer mechanisms include both direct kinetic and potential energy flows.

Abstract

Protein conformational changes are activated processes essential for protein functions. Activation in a protein differs from activation in a small molecule in that it involves directed and systematic energy flows through preferred channels encoded in the protein structure. Understanding the nature of these energy flow channels and how energy flows through them during activation is critical for understanding protein conformational changes. We recently developed a rigorous statistical mechanical framework for understanding potential energy flows. Here we complete this theoretical framework with a rigorous theory for kinetic energy flows: potential and kinetic energy inter-convert when impressed forces oppose inertial forces whereas kinetic energy transfers directly from one coordinate to another when inertial forces oppose each other. This theory is applied to analyzing a prototypic system for biomolecular conformational dynamics: the isomerization of an alanine dipeptide. Among the two essential energy flow channels for this process, dihedral phi confronts the activation barrier, whereas dihedral theta receives energy from potential energy flows. Intriguingly, theta helps phi to cross the activation barrier by transferring to phi via direct kinetic energy flow all the energy it received: increase in theta caused by potential energy flow converts into increase in phi. As a compensation, theta receives kinetic energy from bond angle alpha via direct mechanism and bond angle beta via indirect mechanism.