Computing ensembles of transitions from stable states: Dynamic importance sampling

Juan R. Perilla, Oliver Beckstein, Elizabeth J. Denning, Thomas B Woolf

Research output: Contribution to journalArticle

Abstract

There is an increasing dataset of solved biomolecular structures in more than one conformation and increasing evidence that large-scale conformational change is critical for biomolecular function. In this article, we present our implementation of a dynamic importance sampling (DIMS) algorithm that is directed toward improving our understanding of important intermediate states between experimentally defined starting and ending points. This complements traditional molecular dynamics methods where most of the sampling time is spent in the stable free energy wells defined by these initial and final points. As such, the algorithm creates a candidate set of transitions that provide insights for the much slower and probably most important, functionally relevant degrees of freedom. The method is implemented in the program CHARMM and is tested on six systems of growing size and complexity. These systems, the folding of Protein A and of Protein G, the conformational changes in the calcium sensor S100A6, the glucose-galactose-binding protein, maltodextrin, and lactoferrin, are also compared against other approaches that have been suggested in the literature. The results suggest good sampling on a diverse set of intermediates for all six systems with an ability to control the bias and thus to sample distributions of trajectories for the analysis of intermediate states.

Original languageEnglish (US)
Pages (from-to)196-209
Number of pages14
JournalJournal of Computational Chemistry
Volume32
Issue number2
DOIs
StatePublished - Jan 30 2011

Fingerprint

Importance sampling
Importance Sampling
Ensemble
Sampling
Proteins
Lactoferrin
Computing
Staphylococcal Protein A
Free energy
Protein
Glucose
Conformations
Molecular dynamics
G Protein
Calcium
Trajectories
Folding
Conformation
Molecular Dynamics
Well-defined

Keywords

  • conformational change
  • cooperative motion
  • dynamic importance sampling
  • enhanced sampling
  • kinetics
  • molecular dynamics
  • protein dynamics
  • transition path sampling
  • transition state theory

ASJC Scopus subject areas

  • Chemistry(all)
  • Computational Mathematics

Cite this

Computing ensembles of transitions from stable states : Dynamic importance sampling. / Perilla, Juan R.; Beckstein, Oliver; Denning, Elizabeth J.; Woolf, Thomas B.

In: Journal of Computational Chemistry, Vol. 32, No. 2, 30.01.2011, p. 196-209.

Research output: Contribution to journalArticle

Perilla, Juan R. ; Beckstein, Oliver ; Denning, Elizabeth J. ; Woolf, Thomas B. / Computing ensembles of transitions from stable states : Dynamic importance sampling. In: Journal of Computational Chemistry. 2011 ; Vol. 32, No. 2. pp. 196-209.
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