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Science 23 October 1998:
Vol. 282. no. 5389, pp. 740 - 744
DOI: 10.1126/science.282.5389.740
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Reports

Pathways to a Protein Folding Intermediate Observed in a 1-Microsecond Simulation in Aqueous Solution

Yong Duan, Peter A. Kollman *

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.
*   To whom correspondence should be addressed. E-mail: pak{at}cgl.ucsf.edu

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