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Conformational entropy in molecular recognition by proteins
Author(s) -
Wand A. Joshua
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.528.3
Subject(s) - conformational entropy , calmodulin , entropy (arrow of time) , residual entropy , chemistry , molecular dynamics , protein–protein interaction , computational biology , biophysics , protein structure , biological system , configuration entropy , biology , biochemistry , statistical physics , physics , thermodynamics , molecule , computational chemistry , enzyme , organic chemistry
Molecular recognition by proteins is fundamental to almost every biological process, particularly the protein associations underlying cellular signal transduction. Understanding the basis for protein‐protein interactions requires the full characterization of the thermodynamics of their association. Historically it has been virtually impossible to experimentally assess changes in residual protein entropy, a potentially important component of the change in the binding free energy. NMR spectroscopy has recently emerged as a powerful tool for characterizing the dynamics of proteins and has thereby gained access to their conformational entropy. We have previously shown that the dynamics of calmodulin varies significantly upon binding a variety of target domains. Surprisingly, the apparent change in the corresponding entropy is linearly related to the change in the overall binding entropy. We have completed a complimentary study of the dynamics of the bound calmodulin‐binding domains, which allows for the calibration of the dynamical “entropy meter.” The results indicate that changes in residual protein conformational entropy can indeed contribute significantly to the free energy of protein‐ligand association. This is not a generally held view and has significant implications for the maturation of high affinity interactions either by biological evolution or by human intervention.