In this project, we are using the program DOCK to design new inhibitors of the conformational change of the protein hemagglutinin of influenza virus; these inhibitors could theoretically preclude infection by the virus of the host cell. We are also making progress in the identification of the mode and site of binding of inhibitors designed this way previously by Dale Bodian. These methods will require the extensive use of Computer Graphics Laboratory workstations for programming, running of programs for the coputation of solvent-accessible surfaces of my molecule and identification of potential inhibitor binding sites, and visualization of these sites with graphics programs. We also require visualization of models of inhibitors and of complexes of these inhibitors with hemagglutinin. The MidasPlus program has thus far proven to be extremely useful for these purposes. At this time two potentially interesting sites have been identified using CGL facilities. We have used these sites to design novel inhibitors of hemagglutinin that inhibit infection and I am currently investigating the mode of this inhibition.
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