Computer-aided drug design methodologies are valuable tools that can be used for prediction of the binding mode of small molecules in the three-dimensional structure of a protein. This task becomes more challenging if the ligand is flexible, the case of many known potent inhibitors of HCV NS3A protease. The flexibility of the inhibitors and the fact that the active site of the NS3A protease is flat and featureless makes it difficult to model the designed inhibitors.A docking protocol for the prediction of NS3A protease inhibitors has been developed that includes a Monte Carlo simulation step, a molecular dynamic step and a minimization step. Re-docking experiments using crystallized ligand-protein structures have been used to optimize the parameters. The docking protocol has been applied to a diverse set of synthesized NS3A protease inhibitors in our lab.

Binding mode prediction of HCV NS3A protease inhibitors

244th National Meeting (2012)

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