Nanocomputational Observation of Interaction of Two Cytotoxins and Nanobio Membrane: Molecular Dynamics Simulation Study

Experimental observations have shown that cardio toxins (cobra cytotoxins), small proteins of three-fingered cytotoxin group, damage nanobiomembranes in different cells and vesicles. However, the molecular mechanism of this damage is not yet completely cleared. Molecular dynamics simulations have been used here to study the interaction of cardiotoxins A3 and A4 from Naja atra cobra venom with hydrated 1-palmitoyl-2-oleoyl-1- sn -3-phosphatidylcholine (POPC) lipid bilayer in two separate systems. Each of studied systems included one cytotoxin molecule, 128 lipid molecules (64 molecules in each monolayer) and 11817 water molecules. It has been found that the toxin interacts with zwitterionic bilayer formed by POPC. At the beginning of simulation the cytotoxins have been oriented toward nanobiomembrane surface by their loops’ tips. This orientation has changed during first 50 ns of classical molecular dynamics simulation for both of studied cytotoxins. The A3 toxin finally meets POPC nanobiomembrane with sides of loops near tips including cytotoxin region THR148 and VAL155. The A4 cytotoxin molecule has been finally oriented toward surface of nanobiomembrane with base and one of loop's tip including THR184, ARG186 and LEU158 amino acids, after 50 ns molecular dynamics simulation. Then 25 ns steered molecular dynamics simulation has been done for both of systems. The obtained data suggest that cytotoxin A3 meets the nanobiomembrane with sides of loops near tips and A4 meets POPC nanobiomembrane with base and one of loop's tips. The difference between final orientations of these two cytotoxins comes from the difference in the structure of them.