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Deconstructing thermodynamic parameters of a coupled system from site-specific observables
Journal article   Open access   Peer reviewed

Deconstructing thermodynamic parameters of a coupled system from site-specific observables

Sandipan Chowdhury and Baron Chanda
Proceedings of the National Academy of Sciences - PNAS, Vol.107(44), pp.18856-18861
10/13/2010
DOI: 10.1073/pnas.1003609107
PMCID: PMC2973918
PMID: 20944067
url
https://doi.org/10.1073/pnas.1003609107View
Published (Version of record) Open Access

Abstract

Cooperative interactions mediate information transfer between structural domains of a protein molecule and are major determinants of protein function and modulation. The prevalent theories to understand the thermodynamic origins of cooperativity have been developed to reproduce the complex behavior of a global thermodynamic observable such as ligand binding or enzyme activity. However, in most cases the measurement of a single global observable cannot uniquely define all the terms that fully describe the energetics of the system. Here we establish a theoretical groundwork for analyzing protein thermodynamics using site-specific information. Our treatment involves extracting a site-specific parameter (defined as χ value) associated with a structural unit. We demonstrate that, under limiting conditions, the χ value is related to the direct interaction terms associated with the structural unit under observation and its intrinsic activation energy. We also introduce a site-specific interaction energy term ( χ diff ) that is a function of the direct interaction energy of that site with every other site in the system. When combined with site-directed mutagenesis and other molecular level perturbations, analyses of χ values of site-specific observables may provide valuable insights into protein thermodynamics and structure.
 Biological Sciences cooperativity ion channels protein thermodynamics

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