Sampling of Protein Folding Transitions: Multicanonical Versus Replica Exchange Molecular Dynamics

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Jiang P., YAŞAR F., Hansmann U. H. E.

JOURNAL OF CHEMICAL THEORY AND COMPUTATION, vol.9, no.8, pp.3816-3825, 2013 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 9 Issue: 8
  • Publication Date: 2013
  • Doi Number: 10.1021/ct400312d
  • Journal Name: JOURNAL OF CHEMICAL THEORY AND COMPUTATION
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.3816-3825
  • Hacettepe University Affiliated: Yes

Abstract

We compare the efficiency of multicanonical and replica exchange molecular dynamics for the sampling of folding/unfolding events in simulations of proteins with end-to-end beta-sheet. In Go-model simulations of the 75-residue MNK6, we observe improvement factors of 30 in the number of folding/unfolding events of multicanonical molecular dynamics over replica exchange molecular dynamics. As an application, we use this enhanced sampling to study the folding landscape of the 36-residue DS119 with an all-atom physical force field and implicit solvent. Here, we find that the rate-limiting step is the formation of the central helix that then provides a scaffold for the parallel beta-sheet formed by the two chain ends.