Discrete molecular dynamics: An efficient and versatile simulation method for fine protein characterization

David Shirvanyants, Feng Ding, Douglas Tsao, Srinivas Ramachandran, Nikolay V. Dokholyan

Research output: Contribution to journalArticlepeer-review

166 Scopus citations


Until now it has been impractical to observe protein folding in silico for proteins larger than 50 residues. Limitations of both force field accuracy and computational efficiency make the folding problem very challenging. Here we employ discrete molecular dynamics (DMD) simulations with an all-atom force field to fold fast-folding proteins. We extend the DMD force field by introducing long-range electrostatic interactions to model salt-bridges and a sequence-dependent semiempirical potential accounting for natural tendencies of certain amino acid sequences to form specific secondary structures. We enhance the computational performance by parallelizing the DMD algorithm. Using a small number of commodity computers, we achieve sampling quality and folding accuracy comparable to the explicit-solvent simulations performed on high-end hardware. We demonstrate that DMD can be used to observe equilibrium folding of villin headpiece and WW domain, study two-state folding kinetics, and sample near-native states in ab initio folding of proteins of ∼100 residues.

Original languageEnglish (US)
Pages (from-to)8375-8382
Number of pages8
JournalJournal of Physical Chemistry B
Issue number29
StatePublished - Jul 26 2012

All Science Journal Classification (ASJC) codes

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry


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