Encyclopedia of Biophysics

Living Edition
| Editors: Gordon Roberts, Anthony Watts, European Biophysical Societies

Conformational Entropy

  • A. Joshua Wand
Living reference work entry
DOI: https://doi.org/10.1007/978-3-642-35943-9_10069-1



The entropy associated with the multiplicity of structural states occupied by an ensemble of protein molecules.

The extreme structural complexity of protein molecules has been evident from the very beginning of structural studies at atomic resolution by crystallography, NMR spectroscopy, and, more recently, electron microscopy. In parallel with the subsequent explosion of structural biology were smaller efforts at unraveling the nature of internal dynamics of folded protein molecules. Fundamental theoretical considerations suggested the potential for considerable residual entropy of protein molecules, which will be expressed as fluctuations between different structural states up to and including the globally unfolded state (Cooper 1976; Welch et al. 1982). Thus internal motion is intimately connected to the internal entropy of proteins and has served to shine light on this fundamental component of protein thermodynamics. The internal...

This is a preview of subscription content, log in to check access.


  1. Akke M, Bruschweiler R, Palmer AG III (1993) NMR order parameters and free energy: an analytical approach and its application to cooperative Ca2+ binding by calbindin D9k. J Am Chem Soc 115:9832–9833CrossRefGoogle Scholar
  2. Caro JA, Harpole KW, Kasinath V, Lim J, Granja J, Valentine KG, Sharp KA, Wand AJ (2017) Entropy in molecular recognition by proteins. Proc Natl Acad Sci U S A 114:6563–6568CrossRefPubMedPubMedCentralGoogle Scholar
  3. Cooper A (1976) Thermodynamic fluctuations in protein molecules. Proc Natl Acad Sci U S A 73:2740–2741CrossRefPubMedPubMedCentralGoogle Scholar
  4. Englander SW, Kallenbach NR (1983) Hydrogen exchange and structural dynamics of proteins and nucleic acids. Q Rev Biophys 16:521–655CrossRefPubMedGoogle Scholar
  5. Igumenova TI, Frederick KK, Wand AJ (2006) Characterization of the fast dynamics of protein amino acid side chains using NMR relaxation in solution. Chem Rev 106:1672–1699CrossRefPubMedPubMedCentralGoogle Scholar
  6. Karplus M (2014) Development of multiscale models for complex chemical systems: from H+H2 to biomolecules (Nobel lecture). Angew Chem Int Ed 53:9992–10005CrossRefGoogle Scholar
  7. Karplus M, Ichiye T, Pettitt BM (1987) Configurational entropy of native proteins. Biophys J 52:1083–1085CrossRefPubMedPubMedCentralGoogle Scholar
  8. Lipari G, Szabo A (1982) Model-free approach to the interpretation of nuclear magnetic resonance relaxation in macromolecules. 1. Theory and range of validity. J Am Chem Soc 104:4546–4559CrossRefGoogle Scholar
  9. Li Z, Raychaudhuri S, Wand, AJ (1996) Insights into the local residual entropy of proteins provided by NMR relaxation. Protein Sci 5:2647–2650CrossRefPubMedPubMedCentralGoogle Scholar
  10. Mittermaier A, Kay LE (2006) New tools provide new insights in NMR studies of protein dynamics. Science 312:224–228CrossRefGoogle Scholar
  11. Motlagh HN, Wrabl JO, Li J, Hilser VJ (2014) The ensemble nature of allostery. Nature 508:331–339CrossRefPubMedPubMedCentralGoogle Scholar
  12. O’Brien ES, Wand AJ, Sharp KA (2016) On the ability of molecular dynamics force fields to recapitulate NMR derived protein side chain order parameters. Prot Sci 25:1156–1160CrossRefGoogle Scholar
  13. Wand AJ, Sharp KA (2018) Measuring entropy in molecular recognition by proteins. Annu Rev Biophys 41: in pressGoogle Scholar
  14. Welch GR, Somogyi B, Damjanovich S (1982) The role of fluctuations in enzyme action: a review. Prog Biophys Mol Biol 39:109–146CrossRefPubMedGoogle Scholar
  15. Yang D, Kay LE (1996) Contributions to conformational entropy arising from bond vector fluctuations measured from NMR-derived order parameters: application to protein folding. J Mol Biol 263:369–382CrossRefPubMedGoogle Scholar

Copyright information

© European Biophysical Societies’ Association (EBSA) 2018

Authors and Affiliations

  1. 1.Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA

Section editors and affiliations

  • Alan Cooper
    • 1
  1. 1.School of Chemistry, University of GlasgowGlasgowUK