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arXiv · 2111.02465

Concerted Rolling and Membrane Penetration Revealed by Atomistic Simulations of Antimicrobial Peptides

Jacob M. Remington·Jonathon B. Ferrell·Jianing Li
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Abstract

Short peptides with antimicrobial activity have therapeutic potential for treating bacterial infections. Mechanisms of actions for antimicrobial peptides require binding the biological membrane of their target, which often represents a key mechanistic step. A multitude of data-driven approaches have been developed to predict potential antimicrobial peptide sequences; however, these methods are usually agnostic to the physical interactions between the peptide and the membrane. Towards developing higher throughput screening methodologies, here we use Markov State Modeling and all-atom molecular dynamics simulations to quantify the membrane binding and insertion kinetics of three prototypical and antimicrobial peptides (alpha-helical magainin 2 and PGLa and beta-hairpin tachyplesin 1). By leveraging a set of collective variables that capture the essential physics of the amphiphilic and cationic peptide-membrane interactions we reveal how the slowest kinetic process of membrane insertion is the dynamic rolling of the peptide from a prebound to fully inserted state. These results add critical details to how antimicrobial peptides insert into bacterial membranes.

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Jacob M. Remington, Jonathon B. Ferrell, Jianing Li. 2021-11-03. Concerted Rolling and Membrane Penetration Revealed by Atomistic Simulations of Antimicrobial Peptides. https://arxiv.org/abs/2111.02465

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