Coarse-Grained Molecular Dynamics Simulations of Cobra Cytotoxin A3 Interactions with a Lipid Bilayer: Penetration of Loops into Membranes

Abstract

Cobra cytotoxins, which are small three-looped proteins composed of approximately 60 amino acid residues, primarily act by destroying the bilayer membranes of cells and artificial vesicles. However, the molecular mechanism governing this process is not yet completely understood. We used coarse-grained molecular dynamics (CGMD) simulations to study the mechanism underlying the penetration of cardiotoxin A3 (CTX A3), the major toxic component of Naja atra (Chinese cobra) venom, into a hydrated 1-palmitoyl-2-oleoyl-1-sn-3-phosphatidylcholine (POPC) lipid bilayer. We performed CGMD simulations for three different conformations of the cobra cytotoxin-the tail, lying, and harrow conformations. The results of our simulations indicate that two of these, the tail and lying conformations, did not penetrate the bilayer system. Further, for the harrow conformation, loops 2 and 3 played important roles in penetration of CTX A3 into the bilayer system.