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Free Energy Profiles along Consensus Normal Modes Provide Insight into HIV-1 Protease Flap Opening

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posted on 09.08.2011, 00:00 by Paulo R. Batista, Gaurav Pandey, Pedro G. Pascutti, Paulo M. Bisch, David Perahia, Charles H. Robert
Describing biological macromolecular energetics from computer simulations can pose major challenges, and often necessitates enhanced conformational sampling. We describe the calculation of conformational free-energy profiles along carefully chosen collective coordinates: “consensus” normal modes, developed recently as robust alternatives to conventional normal modes. In an application to the HIV-1 protease, we obtain efficient sampling of significant flap opening movements governing inhibitor binding from relatively short simulations, in close correspondence with experimental results.