A STUDY OF COMBINED STRUCTURE SEQUENCE PROFILES/

Background: For genome sequencing projects to achieve their full impac t on biology and medicine, each protein sequence must be identified wi th its three-dimensional structure. Fold assignment methods (also call ed profile and threading methods) attempt to assign sequences to known protein folds by computing the compatibility of sequence to fold. Res ults: We have extended profile methods for the detection of protein fo lds having structural similarity but low sequence similarity to sequen ce probes. Our extension combines sequence substitution tables with st ructural properties to form a combined profile. The structural propert ies used in this study include distances between residues, exposed are as, areas buried by polar atoms, and properties of the original three- dimensional profile method. We compared the performance of these combi ned profiles with different sequence matrices and with the original th ree-dimensional profile method. To determine the optimal gap penalties and weights used with these profiles, we employed a genetic algorithm . The performance of these combined profiles was tested by cross valid ation using independent test and training sets. Conclusions: These stu dies show that the combined profiles perform better than profiles base d on either structural or sequence information alone. (C) Current Biol ogy Ltd.