Induction of peptide bond dipoles drives cooperative helix formation in the (AAQAA)3 peptide.

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TitleInduction of peptide bond dipoles drives cooperative helix formation in the (AAQAA)3 peptide.
Publication TypeJournal Article
Year of Publication2014
AuthorsHuang, J, Mackerell, AD
JournalBiophys J
Volume107
Issue4
Pagination991-7
Date Published2014 Aug 19
ISSN1542-0086
KeywordsMolecular Dynamics Simulation, Nuclear Magnetic Resonance, Biomolecular, Peptides, Protein Folding, Protein Structure, Secondary, Temperature
Abstract

Cooperativity is a central feature in the formation of secondary structures in proteins. However, the driving forces behind this cooperativity are poorly understood. The present work shows that the cooperativity of helix formation in the acetyl-(AAQAA)3-NH2 peptide is significantly enhanced using an empirical force field that explicitly includes the treatment of electronic polarizability. Polarizable simulations yield helical content consistent with experimental measurements and indicate that the dependence of helical content on temperature is improved over additive models, though further sampling is required to fully validate this conclusion. Cooperativity is indicated by the peptide sampling either the coiled state or long helices with relatively low populations of short helices. The cooperativity is shown to be associated with enhanced dipole moments of the peptide backbone upon helix formation. These results indicate the polarizable force field to more accurately model peptide-folding cooperativity based on its physically realistic treatment of electronic polarizability.

DOI10.1016/j.bpj.2014.06.038
Alternate JournalBiophys. J.
PubMed ID25140435
PubMed Central IDPMC4142245
Grant ListR01 GM072558 / GM / NIGMS NIH HHS / United States
GM051501 / GM / NIGMS NIH HHS / United States
R01 GM051501 / GM / NIGMS NIH HHS / United States
R29 GM051501 / GM / NIGMS NIH HHS / United States
GM072558 / GM / NIGMS NIH HHS / United States