Extending fragment-based free energy calculations with library monte carlo simulation: Annealing in interaction space

Steven Lettieri, Artem B. Mamonov, Daniel M. Zuckerman

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Pre-calculated libraries of molecular fragment configurations have previously been used as a basis for both equilibrium sampling (via library-based Monte Carlo) and for obtaining absolute free energies using a polymer-growth formalism. Here, we combine the two approaches to extend the size of systems for which free energies can be calculated. We study a series of all-atom poly-alanine systems in a simple dielectric solvent and find that precise free energies can be obtained rapidly. For instance, for 12 residues, less than an hour of single-processor time is required. The combined approach is formally equivalent to the annealed importance sampling algorithm; instead of annealing by decreasing temperature, however, interactions among fragments are gradually added as the molecule is grown. We discuss implications for future binding affinity calculations in which a ligand is grown into a binding site.

Original languageEnglish (US)
Pages (from-to)1135-1143
Number of pages9
JournalJournal of Computational Chemistry
Volume32
Issue number6
DOIs
StatePublished - Apr 30 2011

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Keywords

  • annealed importance sampling
  • free energy
  • library-based Monte Carlo
  • library-based growth
  • peptides

ASJC Scopus subject areas

  • Chemistry(all)
  • Computational Mathematics

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