Understanding self-assembling cyclic peptide nanotubes in lipid bilayer by molecular dynamics

COMP 31

Ekta Khurana, ekhurana@sas.upenn.edu, Center for Molecular Modeling, Chemistry Department, University of Pennsylvania, 231 South 34th Street, Philadelphia, PA 19104-6323 and Michael L. Klein, klein@seas.upenn.edu, Department of Chemistry, University of Pennsylvania, 231 S. 34th St., Philadelphia, PA 19104-6323.
Cyclic peptide structures composed of alternating L- and D-a-amino acids self-assemble in a lipid bilayer to form nanotubes, which exhibit ion-channel and antibacterial properties, which are not yet completely understood. Two all atom MD simulations of the tubes, consisting of eight rings and seven rings of cyclo [(-L-Trp-D-Leu-)4-] in DMPC bilayer, with the central axes of the tubes aligned parallel to the normal to the bilayer plane were performed, which showed that a tube consisting of seven rings is stable. The free energy curves for pulling a cation along the central axis of the cyclo [(-L-Trp-D-Leu-)4-] tube were computed for three different heteromeric assemblies, differing only in the capping ring: cyclo [(-L-Trp-D-Leu-)4-], cyclo [(-L-Arg-D-Leu-)4-] and cyclo [(-L-Glu-D-Leu-)4-]. In the carpet-like mode of action for antibacterial activity, the central axis of the tube is aligned perpendicular to the normal to the bilayer plane. Another simulation was performed, with the tube consisting of seven rings placed above the lipid head groups, in the aqueous phase, with the central axis of the tube perpendicular to the normal to the bilayer plane. Our results here provide better understanding of these nanotubes as ion-channels and antibacterial agents.

 

General Oral: Molecular Mechanics and Simulation
8:30 AM-12:05 PM, Sunday, 10 September 2006 Moscone Center -- Room 208/210, Oral

Division of Computers in Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006