Biophysical Society Thematic Meeting | Ascona, Switzerland

Liposomes, Exosomes, and Virosomes: From Modeling Complex Membrane Processes to Medical Diagnostics and Drug Delivery

Poster Abstracts

16-POS Board 8 Multiscale Molecular Dynamics Simulations of Antimicrobial Peptides Chrysophsin-3 in Lipid Bilayers Andrea Catte , Vasily S. Oganesyan. School of Chemistry, University of East Anglia, Norwich, United Kingdom. Antimicrobial peptides (AMPs) are small cationic proteins able to destabilize the lipid bilayer structure through different mechanisms of interaction. In this study, we investigate the processes of peptide aggregation and pore formation by chrysophsin-3 peptides in lipid bilayers and vesicles using multiscale molecular dynamics (MD) simulations. The combination of the long timescale of coarse grained (CG) MD simulations with the high resolution of all atom (AA) MD simulations allows us to study the formation and the structure of pores. In 50 μs CG MD simulations chrysophsin-3 peptides spontaneously interact with the lipid membrane forming distorted toroidal pores and aggregates in palmitoyloleoylphosphatidylcholine (POPC), dipalmitoylphosphatidylcholine (DPPC), and palmitoyloleoylphosphatidylethanolamine (POPE):palmitoyloleoylphosphatidylglycerol (POPG) lipid bilayers and vesicles. Moreover, chrysophsin-3 peptides are also found adsorbed on the lipid membrane. All these different modes of binding of chrysophsin-3 peptides are in agreement with experimental results (1). The AA MD simulation of a POPC lipid bilayer with 50 chrysophsin-3 peptides fine grained from a 16 μs CG structure shows the penetration of water into the lipid bilayer and a reduction of the α-helical content of chrysophsin-3 peptides in agreement with previous computational studies (2). The free energy profile of the insertion of a peptide into the lipid bilayer indicates that the transition from surface adsorbed to transmembrane peptides is associated with a high energy barrier. References 1. Wang, K. F., R. Nagarajan, and T. A. Camesano, Biophys. Chem. 2015, 196, 53-67. 2. Thøgersen, L., B. Schiøtt, T. Vosegaard, N. C. Nielsen, and E. Tajkhorshid, Biophys. J. 2008, 95, 4337-4347.

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