Biophysical Society Thematic Meeting

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.