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

Paulo R Batista (1) , Gaurav Pandey (2) , Pedro G Pascutti (1) , Paulo M Bisch (1) , David Perahia (3) , Charles Robert (2)

1 IBCCF / UFRJ - Instituto de Biofísica Carlos Chagas Filho [Rio de Janeiro]
2 LBT (UPR_9080) - Laboratoire de biochimie théorique [Paris]
3 IBBMC - Institut de biochimie et biophysique moléculaire et cellulaire

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.

Domaines: Biochimie [q-bio.BM]

Paulo R Batista, Gaurav Pandey, Pedro G Pascutti, Paulo M Bisch, David Perahia, et al.. Free Energy Profiles along Consensus Normal Modes Provide Insight into HIV-1 Protease Flap Opening. Journal of Chemical Theory and Computation, 2011, 7 (8), pp.2348-2352. ⟨10.1021/ct200237u⟩. ⟨hal-02988887⟩