Sequence and structure continuity of evolutionary importance improves protein functional site discovery and annotation.

ABSTRACT: Protein functional sites control most biological processes and are important targets for drug design and protein engineering. To characterize them, the evolutionary trace (ET) ranks the relative importance of residues according to their evolutionary variations. Generally, top-ranked residues cluster spatially to define evolutionary hotspots that predict functional sites in structures. Here, various functions that measure the physical continuity of ET ranks among neighboring residues in the structure, or in the sequence, are shown to inform sequence selection and to improve functional site resolution. This is shown first, in 110 proteins, for which the overlap between top-ranked residues and actual functional sites rose by 8% in significance. Then, on a structural proteomic scale, optimized

SUBMITTER: Wilkins AD 

PROVIDER: S-EPMC2974822 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature