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New CHARMM force field parameters for dehydrated amino acid residues, the key to lantibiotic molecular dynamics simulations

Turpin, Eleanor R.; Mulholland, Sam; Teale, Andrew M.; Bonev, Boyan B.; Hirst, Jonathan D.

Authors

Eleanor R. Turpin

Sam Mulholland



Abstract

Lantibiotics are an important class of naturally occurring antimicrobial peptides containing unusual dehydrated amino acid residues. In order to enable molecular dynamics simulations of lantibiotics, we have developed empirical force field parameters for dehydroalanine and dehydrobutyrine, which are compatible with the CHARMM all-atom force field. The parameters reproduce the geometries and energy barriers from MP2/6-31G*//MP2/cc-pVTZ quantum chemistry calculations. Experimental, predicted and calculated NMR chemical shifts for the amino protons and α-, β- and carbonyl carbon atoms of the dehydrated residues are consistent with a significant charge redistribution. The new parameters are used to perform the first molecular dynamics simulations of nisin, a widely used but poorly understood lantibiotic, in an aqueous environment and in a phospholipid bilayer. The simulations show surface association of the peptide with membranes in agreement with solid state NMR data and formation of β-turns in agreement with solution NMR.

Journal Article Type Article
Publication Date Sep 22, 2014
Journal RSC Adv.
Print ISSN 2046-2069
Electronic ISSN 2046-2069
Publisher Royal Society of Chemistry
Peer Reviewed Peer Reviewed
Volume 4
Issue 89
Pages 48621-48631
APA6 Citation Turpin, E. R., Mulholland, S., Teale, A. M., Bonev, B. B., & Hirst, J. D. (2014). New CHARMM force field parameters for dehydrated amino acid residues, the key to lantibiotic molecular dynamics simulations. RSC Advances, 4(89), 48621-48631. https://doi.org/10.1039/c4ra09897h
DOI https://doi.org/10.1039/c4ra09897h
Keywords lantibiotics, antimicrobial peptides
Publisher URL http://pubs.rsc.org/en/Content/ArticleLanding/2014/RA/C4RA09897H#!divAbstract
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf
Additional Information : This document is CrossCheck deposited; : Supplementary Information; : The Royal Society of Chemistry has an exclusive publication licence for this journal; : Received 5 September 2014; Accepted 22 September 2014; Accepted Manuscript published 22 September 2014; Version of Record published 7 October 2014

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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