PubMed ID: 18683277
Author(s): Barzegar A, Moosavi-Movahedi AA, Mahnam K, Bahrami H, Sheibani N. Molecular dynamic simulations of nanomechanic chaperone peptide and effects of in silico His mutations on nanostructured function. J Pept Sci. 2008 Nov;14(11):1173-82. doi: 10.1002/psc.1055. PMID 18683277
Journal: Journal Of Peptide Science : An Official Publication Of The European Peptide Society, Volume 14, Issue 11, Nov 2008
The nanoscale peptide YSGVCHTDLHAWHGDWPLPVK exhibits molecular chaperone activity and prevents protein aggregation under chemical and/or thermal stress. Here, His mutations of this peptide and their impact on chaperone activity were evaluated using theoretical techniques. Molecular dynamic (MD) simulations with simulated annealing (SA) of different mutant nanopeptides were employed to determine the contribution of the scaffolding His residues (H45, H49, H52), when mutated to Pro, on chaperone action in vitro. The in silico mutations of His residues to Pro (H45P, H49P, H52P) revealed loss of secondary ordered strand structure. However, a small part of the strand conformation was formed in the middle region of the native chaperone peptide. The His-to-Pro mutations resulted in decreased gyration radius (Rg) values and surface accessibility of the mutant peptides under the simulation times. The invariant dihedral angle (phi) values and the disrupting effects of the Pro residues indicated the coil conformation of mutant peptides. The failure of the chaperone-like action in the Pro mutant peptides was consistent with their decreased effective accessible surfaces. The high variation of Phi value for His residues in native chaperone peptide leads to high flexibility, such as a minichaperone acting as a nanomachine at the molecular level. Our findings demonstrate that the peptide strand conformation motif with high flexibility at nanoscale is critical for chaperone activity.
Copyright (c) 2008 European Peptide Society and John Wiley & Sons, Ltd.