Antimicrobial peptides (AMPs) act as host defenses against microbial pathogens. Here we investigate the interactions of SVS-1 (KVKVKVKVPPTKVKVKVK), an engineered AMP and anti-cancer β-hairpin peptide, with lipid bilayers using spectroscopic studies and atomistic molecular dynamics simulations. In agreement with literature reports, simulation and experiment show preferential binding of SVS-1 peptides to anionic over neutral bilayers. Fluorescence and circular dichroism studies of a Trp-substituted SVS-1 analogue indicate, however, that it will bind to a zwitterionic DPPC bilayer under high-curvature conditions and folds into a hairpin. In bilayers formed from a 1:1 mixture of DPPC and anionic DPPG lipids, curvature and lipid fluidity are also observed to promote deeper insertion of the fluorescent peptide. Simulations using the CHARMM C36m force field offer complementary insight into timescales and mechanisms of folding and insertion. SVS-1 simulated at an anionic mixed POPC/POPG bilayer folded into a hairpin over a microsecond, the final stage in folding coinciding with the establishment of contact between the peptide's valine sidechains and the lipid tails through a "flip and dip" mechanism. Partial, transient folding and superficial bilayer contact are seen in simulation of the peptide at a zwitterionic POPC bilayer. Only when external surface tension is applied does the peptide establish lasting contact with the POPC bilayer. Our findings reveal the influence of disruption to lipid headgroup packing (via curvature or surface tension) on the pathway of binding and insertion, highlighting the collaborative effort of electrostatic and hydrophobic interactions on interaction of SVS-1 with lipid bilayers.

Metrics & MoreArticle Recommendations T he killings of George Floyd and Breonna Taylor as well as the resulting protests have brought about a time of intense reflection for many people in the United States, including the chemistry community.Being Black in chemistry is a lonely experience for many, and it doesn't get better after earning a PhD. C&EN recently invited six Black chemists working in academia, industry, and government to share their experiences and their hopes for a more equitable future in the sciences. Always the Odd One OutDevin Swiner, graduate student in chemistry, the Ohio State University, and cofounder of #BlackinChem

Peripheral membrane proteins such as the Ras and Src superfamilies go through various post-translational modifications that attach specific amino acids with fatty acid tails. A post-transnationally modified protein can then bind to the bilayer by anchoring itself to it. In our current study, we have used all-atom simulations in the CHARMM36 force field to parameterize four of the more common post-translational modifications into the martini force field -palmitoylated cysteine, farnesylated cysteine, geranylated cysteine and myristoylated glycine. Our process has been designed to reproduce the all-atom bonded parameters and the water-octanol partitioning free energies of these amino acids for the martini force field. Free energy values were obtained through an alchemical reaction coordinate via thermodynamic integration (TI) with the multiple state Bennet acceptance ratio method (MBAR).

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