From Protein Structure to Function with Bioinformatics.pdf

256 R.A. LaskowskiFig. 10.2 Gene Ontology map generated for PDB entry 2fck showing the hierarchy of functionalterms, from the general to the specific. Where ProKnow identifies more than one functional predictionthe map returned will show a network of possibilities, each linked to any others that aresimilar, with the connections colour-coded by the similarity of the termsas the protein almost certainly comprises several structural domains, the boundariesof which would ideally be manually identified. Each domain’s fold has then to berecognized. Even if these stages are successful, the 3D arrangement of the domainsmay be crucial for the protein’s function, and methods to predict domain packingare in their infancy (Wollacott et al. 2007; Berrondo et al. 2008).10.2.2 3D MotifsAfter the fold-matching stage, the protein’s 3D structure is scanned for any 3Dmotifs that are strongly associated with function. These come from the RIGORdatabase of automatically generated structural motifs (Kleywegt 1999). Eachmotif consists of an ‘interesting’ arrangement of residues in a PDB structuralmodel. Three rules distinguish interesting arrangements from uninteresting ones:(a) the protein contains n sequential residues of the same type (e.g. four consecutivearginine residues), (b) a set of neighbouring residues are all hydrophobic, or