Pathways to a protein folding intermediate observed in a 1-microsecond simulation in aqueous solution.
An implementation of classical molecular dynamics on parallel computers of increased efficiency has enabled a simulation of protein folding with explicit representation of water for 1 microsecond, about two orders of magnitude longer than the longest simulation of a protein in water reported to date. Starting with an unfolded state of villin headpiece subdomain, hydrophobic collapse and helix formation occur in an initial phase, followed by conformational readjustments. A marginally stable state, which has a lifetime of about 150 nanoseconds, a favorable solvation free energy, and shows significant resemblance to the native structure, is observed; two pathways to this state have been found.
Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143, USA.
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Duan
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Kollman
D002352:Carrier Proteins / Q000737:chemistry*; D003198:Computer Simulation; D008432:Mathematical Computing; D008840:Microfilament Proteins / Q000737:chemistry*; D008958:Models, Molecular; D016900:Neurofilament Proteins / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013816:Thermodynamics
D002352:Carrier Proteins; D008840:Microfilament Proteins; D016900:Neurofilament Proteins; D010446:Peptide Fragments; C026615:villin; C115223:villin headpiece subdomain peptide