Self assembly of the HIV-1 VPU protein into a pentameric ion channel using a coarse grain model

PHYS 21

Preston B. Moore, p.moore@usip.edu, Department of Chemistry and Biochemistry and West Center for Computational Chemistry and Drug Design, Univeristy of the Sciences in Philadelphia, 600 S 43rd St., Philadelphia, PA 19104 and Russell DeVane, Center for Molecular Modeling, Chemistry Department, University of Pennsylvania, 231 South 34th Street, Philadelphia, PA 19104.
We simulate the self assembly of a pentameter transmembrane oligomeric ion channel of VPU from monomeric units using a novel coarse grain molecular dynamics model. VPU is a 81 residue peptide encoded by the HIV-1 virus which the transmembrain domain (residues 1-28) is believed to form ion channels that facilitate the release of viral particles. The novel CG model has been parameterized using the experimental free energy of transfer of small molecules the represent the atomic moieties and thermodynamic properties. From the initial conditions of monomer transmembrane units within a lipid bilayer or bilayer mimetic consisting of a slab of octanol, we simulate the formation of a homo-oligomeric pentameter ion channel. We find that the self-assembly of the ion-channel occurs in a stepwise fashion instead of a concerted fashion. The structure and dynamics of the final pentameric oligomeric state is compared and contrasted to all-atom models in both DPPC lipid bilayer and a bilayer mimetic of octanol. We find good agreement between the Coarse Grain (CG) model's final structure and all-atom structures obtained previously as well as known experimental results.
 

Biological Ion Channels: From Molecular Structure to Cellular Function
8:15 AM-12:00 PM, Sunday, August 19, 2007 BCEC -- 157B, Oral

Division of Physical Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007