Detection of functionally important regions in "hypothetical proteins" of known structure

Abstract

Structural genomics initiatives provide ample structures of "hypothetical proteins" (i.e., proteins of unknown function) at an ever increasing rate. However, without function annotation, this structural goldmine is of little use to biologists who are interested in particular molecular systems. To this end, we used (an improved version of) the PatchFinder algorithm for the detection of functional regions on the protein surface, which could mediate its interactions with, e.g., substrates, ligands, and other proteins. Examination, using a data set of annotated proteins, showed that PatchFinder outperforms similar methods. We collected 757 structures of hypothetical proteins and their predicted functional regions in the N-Func database. Inspection of several of these regions demonstrated that they are useful for function prediction. For example, we suggested an interprotein interface and a putative nucleotide-binding site. A web-server implementation of PatchFinder and the N-Func database are available at http://patchfinder.tau.ac.il/.