title: Atomistic protein folding simulations on the submillisecond time scale using worldwide distributed computing.
abstract: Atomistic simulations of protein folding have the potential to be a great complement to experimental studies, but have been severely limited by the time scales accessible with current computer hardware and algorithms. By employing a worldwide distributed computing network of tens of thousands of PCs and algorithms designed to efficiently utilize this new many-processor, highly heterogeneous, loosely coupled distributed computing paradigm, we have been able to simulate hundreds of microseconds of atomistic molecular dynamics. This has allowed us to directly simulate the folding mechanism and to accurately predict the folding rate of several fast-folding proteins and polymers, including a nonbiological helix, polypeptide alpha-helices, a beta-hairpin, and a three-helix bundle protein from the villin headpiece. Our results demonstrate that one can reach the time scales needed to simulate fast folding using distributed computing, and that potential sets used to describe interatomic interactions are sufficiently accurate to reach the folded state with experimentally validated rates, at least for small proteins.
authors.affiliation: Department of Chemistry, Stanford University, Stanford, CA 94305-5080, USA. pande@stanford.edu
authors.forename: Vijay S
authors.initials: VS
authors.lastname: Pande
authors.forename: Ian
authors.initials: I
authors.lastname: Baker
authors.forename: Jarrod
authors.initials: J
authors.lastname: Chapman
authors.forename: Sidney P
authors.initials: SP
authors.lastname: Elmer
authors.forename: Siraj
authors.initials: S
authors.lastname: Khaliq
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Larson
authors.forename: Young Min
authors.initials: YM
authors.lastname: Rhee
authors.forename: Michael R
authors.initials: MR
authors.lastname: Shirts
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Snow
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Sorin
authors.forename: Bojan
authors.initials: B
authors.lastname: Zagrovic
mesh_terms: D000465:Algorithms; D002352:Carrier Proteins / Q000737:chemistry; D003198:Computer Simulation; D007700:Kinetics; D008840:Microfilament Proteins / Q000737:chemistry; D008956:Models, Chemical; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000737:chemistry; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D015203:Reproducibility of Results; D012997:Solvents; D013816:Thermodynamics; D013997:Time Factors; D014783:Viscosity
chemical_list: D002352:Carrier Proteins; C029152:G-substrate; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D012997:Solvents; C026615:villin