Recent developments in methodologies for calculating the entropy and free energy of biological systems by computer simulation

Curr Opin Struct Biol. 2007 Apr;17(2):181-6. doi: 10.1016/ Epub 2007 Mar 28.


The Helmholtz free energy, F, plays an important role in proteins because of their rugged potential energy surface, which is 'decorated' with a tremendous number of local wells (denoted microstates, m). F governs protein folding, whereas differences DeltaF(mn) determine the relative populations of microstates that are visited by a flexible cyclic peptide or a flexible protein segment (e.g. a surface loop). Recently developed methodologies for calculating DeltaF(mn) (and entropy differences, DeltaS(mn)) mainly use thermodynamic integration and calculation of the absolute F; interesting new approaches in these categories are the adaptive integration method and the hypothetical scanning molecular dynamics method, respectively.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Computer Simulation*
  • Entropy
  • Models, Biological*
  • Multiprotein Complexes / chemistry
  • Protein Folding
  • Systems Biology*
  • Thermodynamics*


  • Multiprotein Complexes