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

J Chem Theory Comput. 2011 Aug 9;7(8):2348-52. doi: 10.1021/ct200237u. Epub 2011 Jul 7.

Abstract

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.