The VP1 protein of the poliovirus capsid contains a fi-barrel witha hollow pocket, inside of which resides a lipid-like ligand, modelled as sphingosine.During the normal infection process, thesphingosine may leave the pocket, altering the stability of thevirus. This process may be prevented by antiviral drugs whichreplace sphingosine [83].At present it is not understood howthe various ligands affect the viral stability and we have initiated molecular dynamics (MD) simulations to uncover this mechanism.It is hypothesized that when the sphingosine leaves the pocketthe capsid swells, and thereby creates windows through whichthe viral RNA can exit to infect the cell. In our study we haveemployed the structure of the poliovirus protomer (P1/Mahonystrain [84]) obtained from the Protein Data Bank.The X-ray structure contains four unresolved sections, which we have predicted from homology data. Using NAMD and X-PLOR , we combined the protomers around a five-fold axis to form a pentamerand minimized the structure. To reduce the system size, we cuta 60 A sphere (containing 30,000 atoms, waters not included)around the five-fold axis. Presently, we are carrying out an MDsimulation to observe the possible conformational rearrangementinduced by removal of the sphingosine substrate. Also, the capsid structures of poliovirus P3/Sabin strain with and without thedrug disoxaril bound have recently become available and can beused to further study the structural changes in the VP1 beta barrel caused by replacing the sphingosine with various drugs. We intend to measure the effect of these changes on the interaction of VP1 with its neighboring proteins.
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