Conformational entropy in molecular recognition by proteins

Kendra King Frederick, Michael S. Marlow, Kathleen G. Valentine, A. Joshua Wand

Research output: Contribution to journalArticle

457 Scopus citations

Abstract

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 estimate changes in protein conformational entropy, a potentially important component of the free energy of protein association. However, nuclear magnetic resonance spectroscopy has emerged as a powerful tool for characterizing the dynamics of proteins. Here we employ changes in conformational dynamics as a proxy for corresponding changes in conformational entropy. We find that the change in internal dynamics of the protein calmodulin varies significantly on binding a variety of target domains. Surprisingly, the apparent change in the corresponding conformational entropy is linearly related to the change in the overall binding entropy. This indicates that changes in protein conformational entropy can contribute significantly to the free energy of protein-ligand association.

Original languageEnglish (US)
Pages (from-to)325-329
Number of pages5
JournalNature
Volume448
Issue number7151
DOIs
StatePublished - Jul 19 2007

ASJC Scopus subject areas

  • General

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    Frederick, K. K., Marlow, M. S., Valentine, K. G., & Wand, A. J. (2007). Conformational entropy in molecular recognition by proteins. Nature, 448(7151), 325-329. https://doi.org/10.1038/nature05959