The allostery landscape: quantifying thermodynamic couplings in biomolecular systems

TL;DR

This paper introduces a statistical mechanical framework to quantify allosteric couplings in biomolecular systems as a two-dimensional thermodynamic function, linking it to information theory and enabling mechanistic insights.

Contribution

It develops a novel thermodynamic coupling function for allostery, extending beyond two-state models, and demonstrates its application in analyzing biomolecular interactions.

Findings

Allosteric coupling is represented by a two-dimensional thermodynamic function.

The method links thermodynamic coupling to mutual information and copula density.

Application to alanine dipeptide reveals key interactions for allostery.

Abstract

Allostery plays a fundament role in most biological processes. However, little theory is available to describe it outside of two-state models. Here we use a statistical mechanical approach to show that the allosteric coupling between two collective variables is not a single number, but instead a two-dimensional thermodynamic coupling function that is directly related to the mutual information from information theory and the copula density function from probability theory. On this basis, we demonstrate how to quantify the contribution of specific energy terms to this thermodynamic coupling function, enabling a decomposition that reveals the mechanism of allostery. We illustrate the thermodynamic coupling function and its use by showing how allosteric coupling in the alanine dipeptide molecule contributes to the overall shape of the {\Phi}/{\Psi} free energy surface, and by identifying the interactions that are necessary for this coupling.