Visualisation of variable binding pockets on protein surfaces by probabilistic analysis of related structure sets.

ABSTRACT:

Background

Protein structures provide a valuable resource for rational drug design. For a protein with no known ligand, computational tools can predict surface pockets that are of suitable size and shape to accommodate a complementary small-molecule drug. However, pocket prediction against single static structures may miss features of pockets that arise from proteins' dynamic behaviour. In particular, ligand-binding conformations can be observed as transiently populated states of the apo protein, so it is possible to gain insight into ligand-bound forms by considering conformational variation in apo proteins. This variation can be explored by considering sets of related structures: computationally generated conformers, solution NMR ensembles, multiple crystal structures, homologues

SUBMITTER: Ashford P 

PROVIDER: S-EPMC3359218 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature