Characterization of the free-energy landscapes of proteins by NMR-guided metadynamics.

ABSTRACT: The use of free-energy landscapes rationalizes a wide range of aspects of protein behavior by providing a clear illustration of the different states accessible to these molecules, as well as of their populations and pathways of interconversion. The determination of the free-energy landscapes of proteins by computational methods is, however, very challenging as it requires an extensive sampling of their conformational spaces. We describe here a technique to achieve this goal with relatively limited computational resources by incorporating nuclear magnetic resonance (NMR) chemical shifts as collective variables in metadynamics simulations. As in this approach the chemical shifts are not used as structural restraints, the resulting free-energy landscapes correspond to the force fields used in

SUBMITTER: Granata D 

PROVIDER: S-EPMC3637744 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature