Extending fragment-based free energy calculations with library monte carlo simulation

Annealing in interaction space

Steven Lettieri, Artem B. Mamonov, Daniel Zuckerman

Research output: Contribution to journalArticle

5 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Annealing
Free energy
Free Energy
Fragment
Monte Carlo Simulation
Interaction
Importance sampling
Importance Sampling
Binding sites
Alanine
Affine transformation
Polymers
Binding Sites
Ligands
Molecules
Sampling
Atoms
Configuration
Series
Libraries

Keywords

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

ASJC Scopus subject areas

  • Chemistry(all)
  • Computational Mathematics

Cite this

Extending fragment-based free energy calculations with library monte carlo simulation : Annealing in interaction space. / Lettieri, Steven; Mamonov, Artem B.; Zuckerman, Daniel.

In: Journal of Computational Chemistry, Vol. 32, No. 6, 30.04.2011, p. 1135-1143.

Research output: Contribution to journalArticle

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