Escaping free-energy minima

Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12562-6. doi: 10.1073/pnas.202427399. Epub 2002 Sep 23.


We introduce a powerful method for exploring the properties of the multidimensional free energy surfaces (FESs) of complex many-body systems by means of coarse-grained non-Markovian dynamics in the space defined by a few collective coordinates. A characteristic feature of these dynamics is the presence of a history-dependent potential term that, in time, fills the minima in the FES, allowing the efficient exploration and accurate determination of the FES as a function of the collective coordinates. We demonstrate the usefulness of this approach in the case of the dissociation of a NaCl molecule in water and in the study of the conformational changes of a dialanine in solution.

MeSH terms

  • Alanine / chemistry
  • Chemistry / methods*
  • Models, Statistical
  • Normal Distribution
  • Sodium Chloride / chemistry
  • Thermodynamics*
  • Water / chemistry


  • Water
  • Sodium Chloride
  • Alanine