Steered molecular dynamics simulations of cobra cytotoxin interaction with zwitterionic lipid bilayer: no penetration of loop tips into membranes

Comput Biol Chem. 2009 Feb;33(1):29-32. doi: 10.1016/j.compbiolchem.2008.07.018. Epub 2008 Jul 18.

Abstract

Cobra cytotoxins, small proteins of three-fingered toxin family, unspecifically damage membranes in different cells and artificial vesicles. However, the molecular mechanism of this damage is not yet completely understood. We used steered molecular dynamics simulations to study the interaction of cardiotoxin A3 from Naja atra cobra venom with hydrated 1-palmitoyl-2-oleoyl-1-sn-3-phosphatidylcholine (POPC) bilayer. The studied system included one cytotoxin molecule, 64 lipid molecules (32 molecules in each monolayer) and 2500 water molecules. It was found that the toxin interacted with zwitterionic bilayer formed by POPC. During first nanosecond of simulation the toxin molecule was oriented toward membrane surface by loops' basement including cytotoxin regions Cys14-Asn19 and Cys38-Ser46. This orientation was stable enough and was not changed during next 6 ns of simulation. The obtained data suggest that cytotoxin molecule cannot penetrate into membrane composed of zwitterionic lipids without some auxiliary interaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cobra Cardiotoxin Proteins / chemistry*
  • Ions
  • Lipid Bilayers*
  • Models, Molecular*
  • Thermodynamics

Substances

  • Cobra Cardiotoxin Proteins
  • Ions
  • Lipid Bilayers