Speaker Biography

N.K.Wijesiri

University of Connecticut

Title: Synergism of Cell Penetrating Peptides in translocating lipid bilayers

N.K.Wijesiri
Biography:

Obtained the B.Sc. (Honors) in Chemistry from the University of Peradeniya (Sri Lanka) in 2019.

As an undergraduate worked on a computational research project with Dr. R.J.K.U. Ranatunga on Molecular docking and cell penetrating peptides as drug delivery agents. Joined Prof. Jose Gascon’s laboratory at University of Connecticut (USA) in 2019 to pursue a Ph.D. Currently focusing on siRNA therapeutics and Molecular Modeling of Monolayer Protected Gold Clusters used as biosensors and drug delivery agents.

 

Abstract:

A major difficulty faced in administering active molecules as therapeutic agents is their inability to reach specified target sites. Discovery of cell penetrating peptides (CPPs) represent a potential breakthrough for the transport of a range of biological cargos. CPPs, which are small peptidic molecules capable of translocating through cell membranes, have received significant attention due to their low cytotoxicity and high transduction efficiency. They are classified as cationic, amphipathic and hydrophobic depending on their physicochemical characteristics. Permeation mechanisms of CPPs are not fully understood. There is evidence for both energy dependent and energy independent pathways.

Here we study four CPPs (penetratin, C6, transportan, and K-FGF) to investigate the effect of synergism of multiple peptides in translocation through DOPC bilayers. Results of all-atom Molecular Dynamics (MD) computer simulations show that all CPPs have stable α-helical secondary structures. Moreover, translocation free energy profiles for a single peptide and multi-peptide systems were constructed through coarse grained MD simulations. Free energy profiles indicate that all CPPs spontaneously adsorb on to the surface of the bilayer and the synergism facilitates the spontaneous adsorption. Furthermore, although none of the peptides showed spontaneous translocation for individual peptides, in the case of C6 and K-FGF, synergism has facilitated translocation by reducing the energy barrier.