Computational approaches to understanding membrane biophysics
and the development of membrane-active therapeutics.
Atomistic Molecular Dynamics Simualtions
We use all-atom molecular dynamics simualtion to study the properties of lipid bilayers and their interactions with peptides. These simulations are on the order of microseconds, and can sample a broad range of properties. Below are examples of the different membrane-bound structures peptides can have. Each movie compares the peptides alamethicin and piscidin 1. Alamethicin is a known pore forming peptide that has an unstable surface-bound structure. In contrast, piscidin 1 has a very stable helical surface-bound structure. More details on the simualtions and their corresponding manuscripts are included on the PerrinResearch YouTube channel. Doenload a high-resolution version of the full proe movie here.
Piscidin. We have worked with Prof. Myriam Cotten to determine the surface-bound state of piscidin 1 and piscidin 3 (Perrin et al. 2014). We also correlated the depth of peptide insertion to the intrinsic curvature induction, and demonstrated that negative curvature induction occurs in peptides with short acyl chains (14 carbons in length, Perrin et al. 2015). In membranes componsed of lipids with longer acyl chains (~16 to 18 carbons), positive curvature is induced.
Peptides that Inhibit HIV transmission - Coming soon
Enhanced Sampling Methods In many cases, these timescales are too short, so we have used and developed enhanced simulation methods to accelerate sampling. More coming soon.