folding very short peptides using molecular dynamics使用分子动力学折短肽.pdfVIP

Folding Very Short Peptides Using Molecular Dynamics * Bosco K. Ho , Ken A. Dill Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, United States of America Peptides often have conformational preferences. We simulated 133 peptide 8-mer fragments from six different proteins, sampled by replica-exchange molecular dynamics using Amber7 with a GB/SA (generalized-Born/solvent- accessible electrostatic approximation to water) implicit solvent. We found that 85 of the peptides have no preferred structure, while 48 of them converge to a preferred structure. In 85% of the converged cases (41 peptides), the structures found by the simulations bear some resemblance to their native structures, based on a coarse-grained backbone description. In particular, all seven of the b hairpins in the native structures contain a fragment in the turn that is highly structured. In the eight cases where the bioinformatics-based I-sites library picks out native-like structures, the present simulations are largely in agreement. Such physics-based modeling may be useful for identifying early nuclei in folding kinetics and for assisting in protein-structure prediction methods that utilize the assembly of peptide fragments. Citation: Ho BK, Dill KA (2006) Folding very short peptides using molecular dynamics. PLoS Comput Biol 2(4): e27. DOI: 10.1371/journal.pcbi.0020027 Introduction Here, we study 133 peptide 8-mer fragments from six different proteins of different folds, using replica-exchange Peptide fragments of proteins often have intrinsic propen-