From Protein Structure to Function with Bioinformatics.pdf

12 Prediction of Protein Function from Theoretical Models 309Fig. 12.4 A confirmed structure prediction from Malstrom et al. (2007). The model of TRS20/YBR254C (a) was matched to the SNARE superfamily in the SCOP database, an assignment latervalidated by a later experimental structure (PDB code 1h3q) of a related protein (b) Colours areused for structurally matched regions, grey elsewhereexample of a prediction, that the structure of protein TRS20/YBR254C belongs inthe SNARE superfamily of the SCOP database, that was later confirmed by thedetermination of an experimental structure. The match between model and crystalstructure is partial and limited (Fig. 12.4), illustrating the value of including GOinformation for target and superfamilies of putatively matched structures. In thiscase, the target TRS20/YBR254C is one of the subunits of the transport proteinparticle (TRAPP) complex involved in vesicle docking and fusion. Its match withstructures from the SNARE-like superfamily of SCOP was therefore strongly supportedsince vesicle trafficking is a strong theme of proteins in that superfamily.12.4.5 Prediction of Ligand SpecificityOne of the most basic function predictions that can be obtained from a proteinmodel is ligand specificity. Frequently, if the structure of protein A bound to ligandX is known, it is of interest to predict whether protein B, homologous to A, sharesthe same specificity as X, or in fact binds a different ligand Y. These analyses relyon the assumption that the binding sites of A and B are similarly positioned. Thisis usually the case between homologous proteins and the presence of key catalyticresidues nearby, in the case for enzymes, often offers confirmation. A comparativemodel is then made B, based on the structure of A. Examination of the modelled Bstructure, and in particular its comparison with the template A, should showwhether the binding site appears to have changed. A reduction in size, for example,would lead to the prediction of a smaller ligand.