This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wu, X. Articles by Brooks, B. R. Search for Related Content PubMed PubMed Citation Articles by Wu, X. Articles by Brooks, B. R.

ß-Hairpin Folding Mechanism of a Nine-Residue Peptide Revealed from Molecular Dynamics Simulations in Explicit Water

Laboratory of Biophysical Chemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland

Correspondence: Address reprint requests to Xiongwu Wu, PhD, Laboratory of Biophysical Chemistry, NHLBI, NIH, Bldg. 50, Rm. 3308, 50 South Dr., Bethesda, MD 20892. Tel.: 301-451-6251; Fax: 301-402-3404; E-mail: wuxw{at}nhlbi.nih.gov.

The ß-hairpin fold mechanism of a nine-residue peptide, which is modified from the ß-hairpin of -amylase inhibitor tendamistat (residues 15–23), is studied through direct folding simulations in explicit water at native folding conditions. Three 300-nanosecond self-guided molecular dynamics (SGMD) simulations have revealed a series of ß-hairpin folding events. During these simulations, the peptide folds repeatedly into a major cluster of ß-hairpin structures, which agree well with nuclear magnetic resonance experimental observations. This major cluster is found to have the minimum conformational free energy among all sampled conformations. This peptide also folds into many other ß-hairpin structures, which represent some local free energy minimum states. In the unfolded state, the N-terminal residues of the peptide, Tyr-1, Gln-2, and Asn-3, have a confined conformational distribution. This confinement makes ß-hairpin the only energetically favored structure to fold. The unfolded state of this peptide is populated with conformations with non-native intrapeptide interactions. This peptide goes through fully hydrated conformations to eliminate non-native interactions before folding into a ß-hairpin. The folding of a ß-hairpin starts with side-chain interactions, which bring two strands together to form interstrand hydrogen bonds. The unfolding of the ß-hairpin is not simply the reverse of the folding process. Comparing unfolding simulations using MD and SGMD methods demonstrate that SGMD simulations can qualitatively reproduce the kinetics of the peptide system.

This article has been cited by other articles:

				B. A. Patel, P. G. Debenedetti, F. H. Stillinger, and P. J. Rossky A Water-Explicit Lattice Model of Heat-, Cold-, and Pressure-Induced Protein Unfolding Biophys. J., December 15, 2007; 93(12): 4116 - 4127. [Abstract] [Full Text] [PDF]

				S. Oyama Jr., P. Pristovsek, L. Franzoni, T. A. Pertinhez, E. Schinina, C. Lucke, H. Ruterjans, E. C. Arantes, and A. Spisni Probing the pH-dependent structural features of {alpha}-KTx12.1, a potassium channel blocker from the scorpion Tityus serrulatus Protein Sci., April 1, 2005; 14(4): 1025 - 1038. [Abstract] [Full Text] [PDF]