Identification of family-specific residue packing motifs and their use for structure-based protein function prediction: I. Method development.

Bandyopadhyay, Deepak; Jun Huan; Prins, Jan; Snoeyink, Jack; Wei Wang; Tropsha, Alexander

Protein function prediction is one of the central problems in computational biology. We present a novel automated protein structure-based function prediction method using libraries of local residue packing patterns that are common to most proteins in a known functional family. Critical to this approach is the representation of a protein structure as a graph where residue vertices (residue name used as a vertex label) are connected by geometrical proximity edges. The approach employs two steps. First, it uses a fast subgraph mining algorithm to find all occurrences of family-specific labeled subgraphs for all well characterized protein structural and functional families. Second, it queries a new structure for occurrences of a set of motifs characteristic of a known family, using a graph index to speed up Ullman’s subgraph isomorphism algorithm. The confidence of function inference from structure depends on the number of family-specific motifs found in the query structure compared with their distribution in a large non-redundant database of proteins. This method can assign a new structure to a specific functional family in cases where sequence alignments, sequence patterns, structural superposition and active site templates fail to provide accurate annotation.

PROTEIN structure; GRAPHIC methods; COMPUTATIONAL biology; ALGORITHMS; ISOMORPHISM (Mathematics); GENOMICS

Journal of Computer-Aided Molecular Design, 2009, Vol 23, Issue 11, p773

0920-654X

Academic Journal

10.1007/s10822-009-9273-4