1. Concerted Rolling and Membrane Penetration Revealed by Atomistic Simulations of Antimicrobial Peptides
- Author
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Remington, Jacob M., Ferrell, Jonathon B., and Li, Jianing
- Subjects
Quantitative Biology - Biomolecules ,Physics - Biological Physics - 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.
- Published
- 2021