Free energy analyses of cell penetrating peptides using the weighted ensemble method


Cell penetrating peptides (CPPs) have been widely used for drug-delivery agents, however, it has not been fully understood how they translocate across cell membranes. The Weighted Ensemble (WE) method, one of powerful and flexible path sampling techniques, can be useful to reveal translocation paths and free energy barriers along those paths. Within the WE approach we show how Arg9s (nona-arginine) and Tat interact with a DOPC:DOPG (4:1) model membrane and we also present free energy profiles (or potential of mean forces, PMFs) of translocation across the membrane. A different composition of lipid molecules was also tried and compared. Our approach can be applied to any CPPs interacting with various model membranes and it will provide useful information regarding the transport mechanisms of CPPs.

KPS fall meeting (10/20-10/22, virtual)