Solution conformation of phakellistatin 8 investigated by molecular dynamics simulations.

TitleSolution conformation of phakellistatin 8 investigated by molecular dynamics simulations.
Publication TypeJournal Article
Year of Publication1999
AuthorsGalzitskaya O., Caflisch A.
JournalJournal of Molecular Graphics and Modelling
Volume17
Issue1
Pagination19-27
Date Published1999 Feb
Type of ArticleResearch Article
ISSN1093-3263
KeywordsAntineoplastic Agents, Computer Simulation, Crystallography, X-Ray, Hydrogen Bonding, Models, Molecular, Peptides, Cyclic, Protein Conformation, Protein Structure, Secondary, Software
Abstract

Phakellistatin 8 is a cyclic decapeptide that inhibits cancer cell growth and has sequence and structure similar to antamanide. In molecular dynamics simulations of phakellistatin 8 in water, the decapeptide ring undergoes a conformational change from the saddle-like crystal structure to a more elongated conformation by a transition of the Tyr9 main chain from the alpha L to an extended structure. This is coupled to the loss of the NH9-O6 β-turn hydrogen bond and the transient dissociation of the Pro7-Tyr9 side-chain packing. Furthermore, the water molecule acting as a transannular bridge forms an additional hydrogen bond with phakellistatin 8, namely with the NH group of Val5 besides those already present in the crystal structure, i.e., with the NH of Ile10 and the CO of Leu6. The α-turn hydrogen bond between the Phe4 amide hydrogen and the Ile10 carbonyl oxygen is always present. The solution conformations of the two cyclic decapeptides are similar, in particular in the region involving the NH4-O10 alpha turn of phakellistatin 8 and the NH5-O1 alpha turn of antamanide. The simulation results suggest that in aqueous solution the conformation of phakellistatin 8 is more extended than in the crystalline state, and on a nanosecond time scale phakellistatin 8 is more flexible than antamanide.

DOI10.1016/S1093-3263(99)00017-0
pubindex

0017

Alternate JournalJ. Mol. Graph. Model.
PubMed ID10660907
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