Computing free-energy profiles using multidimensional potentials of mean force and polynomial quadrature methods

Jonah Z. Vilseck, Orlando Acevedo

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

The accurate calculation of free-energy profiles for condensed-phase and enzymatic reactions is often computationally demanding when employing traditional methods such as a combined quantum and molecular mechanical (QM/MM) simulation featuring configurational sampling. A novel polynomial fitting and analytical integration method was recently developed for proton transfer reactions that provides a seven-fold enhancement to the calculation speed compared with traditional potentials of mean force (PMF) methods and yields close agreement with experimental free energies of activation. In addition, the expansion of PMF simulations to monitor three simultaneous reaction coordinates was also reported to enhance phase space sampling, which is useful for accurately elucidating complex reaction mechanisms. This review focuses upon the development of these methods and their utility is illustrated in recent examples including hydrolysis reactions in fatty acid amide hydrolase, Kemp elimination reactions in antibody 4B2 and ionic liquid environments, and condensed-phase singlet oxygen ene reactions.

Original languageEnglish (US)
Pages (from-to)37-49
Number of pages13
JournalAnnual Reports in Computational Chemistry
Volume6
Issue numberC
DOIs
StatePublished - 2010
Externally publishedYes

Keywords

  • Free-energy perturbation
  • Free-energy profiles
  • Polynomial
  • Potentials of mean force
  • QM/MM calculations

ASJC Scopus subject areas

  • Chemistry(all)
  • Computational Mathematics

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