Molecular Dynamics Investigation into the Effect of Zinc(II) on the Structure and Membrane Interactions of the Antimicrobial Peptide Clavanin A

Searle S. Duay, Gaurav Sharma, Rajeev Prabhakar, Alfredo M. Angeles-Boza, Eric R. May

Research output: Contribution to journalArticle

Abstract

Clavanin A (ClavA) is an antimicrobial peptide (AMP) whose antimicrobial activity is enhanced in the presence of Zn(II) ions. The antimicrobial activity of ClavA has been shown to increase 16-fold in the presence of Zn(II) ions. In this study, we investigate the potential sources of this enhancement, namely, the effect of Zn(II) binding on the helical conformation of ClavA and on the ClavA interaction with a model for gram-negative bacterial membranes. In addition, we investigate the effect of Zn(II) on the membrane mechanical properties. We employed all-atom equilibrium molecular dynamics simulations initiated from both fully helical and random coil structures of ClavA. We observe that Zn(II) can stabilize an existing helical conformation in the Zn(II)-binding region, but we do not observe induction of helical conformations in systems initiated in random coil configurations. Zn(II) binding to ClavA provides more favorable electrostatics for membrane association in the C-terminal region. This is evidenced by longer and stronger C-terminal-lipid interactions. Zn(II) is also capable of modulating the membrane properties in a manner which favors ClavA insertion and the potential for enhanced translocation into the cell. This work provides insights into the role of divalent metal cations in the antimicrobial activity of ClavA. This information can be used for the development of synthetic AMPs containing motifs that can bind metals (metalloAMPs) for therapeutic and medical purposes.

Original languageEnglish (US)
Pages (from-to)3163-3176
Number of pages14
JournalJournal of Physical Chemistry B
Volume123
Issue number15
DOIs
StatePublished - Apr 18 2019

Fingerprint

Molecular Dynamics Simulation
Peptides
peptides
Molecular dynamics
Zinc
zinc
molecular dynamics
membranes
Membranes
Conformations
coils
interactions
adenosine monophosphate
Ions
Lipids
lipids
insertion
Electrostatics
induction
ions

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry

Cite this

Molecular Dynamics Investigation into the Effect of Zinc(II) on the Structure and Membrane Interactions of the Antimicrobial Peptide Clavanin A. / Duay, Searle S.; Sharma, Gaurav; Prabhakar, Rajeev; Angeles-Boza, Alfredo M.; May, Eric R.

In: Journal of Physical Chemistry B, Vol. 123, No. 15, 18.04.2019, p. 3163-3176.

Research output: Contribution to journalArticle

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