The Allostery Landscape: Quantifying Thermodynamic
Couplings in Biomolecular Systems

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Abstract

Allostery plays a fundamental 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 an approximate 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 Φ/Ψ free energy surface, and by identifying the interactions that are necessary for this coupling.

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Author and article information

Journal

Journal ID (nlm-ta): J Chem Theory Comput

Journal ID (iso-abbrev): J Chem Theory Comput

Journal ID (publisher-id): ct

Journal ID (coden): jctcce

Title: Journal of Chemical Theory and Computation

Publisher: American Chemical Society

ISSN (Print): 1549-9618

ISSN (Electronic): 1549-9626

Publication date (Electronic): 21 October 2016

Publication date (Print): 13 December 2016

Volume: 12

Issue: 12

Pages: 5758-5767

Affiliations

[1] ^†Department of Physiology and Biophysics and ^§HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medical College of Cornell University , New York, New York 10065, United States

[‡ ]Swiss Institute of Bioinformatics, UNIL Sorge, 1015 Lausanne, Switzerland

Author notes

[* ]E-mail: mil2037@ 123456med.cornell.edu .

Article

DOI: 10.1021/acs.jctc.6b00841

PMC ID: 5156960

PubMed ID: 27766843

SO-VID: 7223d6bb-ac68-44be-9833-5001e487258d

License:

This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.