Ab Initio Folding of Proteins with All-Atom Discrete Molecular Dynamics

Feng Ding, Douglas Tsao, Huifen Nie, Nikolay Dokholyan

Research output: Contribution to journalArticle

197 Scopus citations

Abstract

Discrete molecular dynamics (DMD) is a rapid sampling method used in protein folding and aggregation studies. Until now, DMD was used to perform simulations of simplified protein models in conjunction with structure-based force fields. Here, we develop an all-atom protein model and a transferable force field featuring packing, solvation, and environment-dependent hydrogen bond interactions. We performed folding simulations of six small proteins (20-60 residues) with distinct native structures by the replica exchange method. In all cases, native or near-native states were reached in simulations. For three small proteins, multiple folding transitions are observed, and the computationally characterized thermodynamics are in qualitative agreement with experiments. The predictive power of all-atom DMD highlights the importance of environment-dependent hydrogen bond interactions in modeling protein folding. The developed approach can be used for accurate and rapid sampling of conformational spaces of proteins and protein-protein complexes and applied to protein engineering and design of protein-protein interactions.

Original languageEnglish (US)
Pages (from-to)1010-1018
Number of pages9
JournalStructure
Volume16
Issue number7
DOIs
StatePublished - Jul 9 2008

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

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