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.

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.

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

• Journal Article Type: Article
• Acceptance Date: Sep 22, 2014
• Online Publication Date: Sep 22, 2014
• Publication Date: Sep 22, 2014
• Deposit Date: Dec 16, 2015
• Publicly Available Date: Dec 16, 2015
• Journal: RSC Adv.
• Electronic ISSN: 2046-2069
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 4
• Issue: 89
• Pages: 48621-48631
• DOI: https://doi.org/10.1039/c4ra09897h
• Keywords: lantibiotics, antimicrobial peptides
• Public URL: https://nottingham-repository.worktribe.com/output/735568
• Publisher URL: http://pubs.rsc.org/en/Content/ArticleLanding/2014/RA/C4RA09897H#!divAbstract
• 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
• Contract Date: Dec 16, 2015