Improvement in protein functional site prediction by distinguishing structural and functional constraints on protein family evolution using computational design.

ABSTRACT: The prediction of functional sites in newly solved protein structures is a challenge for computational structural biology. Most methods for approaching this problem use evolutionary conservation as the primary indicator of the location of functional sites. However, sequence conservation reflects not only evolutionary selection at functional sites to maintain protein function, but also selection throughout the protein to maintain the stability of the folded state. To disentangle sequence conservation due to protein functional constraints from sequence conservation due to protein structural constraints, we use all atom computational protein design methodology to predict sequence profiles expected under solely structural constraints, and to compute the free energy difference between the natur

SUBMITTER: Cheng G 

PROVIDER: S-EPMC1258172 | biostudies-literature | 2005

REPOSITORIES: biostudies-literature