title: Comparison of non-sequential sets of protein residues.
abstract: A methodology for performing sequence-free comparison of functional sites in protein structures is introduced. The method is based on a new notion of similarity among superimposed groups of amino acid residues that evaluates both geometry and physico-chemical properties. The method is specifically designed to handle disconnected and sparsely distributed sets of residues. A genetic algorithm is employed to find the superimposition of protein segments that maximizes their similarity. The method was evaluated by performing an all-to-all comparison on two separate sets of ligand-binding sites, comprising 47 protein-FAD (Flavin-Adenine Dinucleotide) and 64 protein-NAD (Nicotinamide-Adenine Dinucleotide) complexes, and comparing the results with those of an existing sequence-based structural alignment tool (TM-Align). The quality of the two methodologies is judged by the methods' capacity to, among other, correctly predict the similarities in the protein-ligand contact patterns of each pair of binding sites. The results show that using a sequence-free method significantly improves over the sequence-based one, resulting in 23 significant binding-site homologies being detected by the new method but ignored by the sequence-based one.
authors.affiliation: Biocenter Oulu, and Faculty of Biochemistry and Molecular Medicine, University of Oulu, PO Box 5400, FI-90014 Oulu, Finland.
authors.forename: Leonardo D
authors.initials: LD
authors.lastname: Garma
authors.affiliation: Biocenter Oulu, and Faculty of Biochemistry and Molecular Medicine, University of Oulu, PO Box 5400, FI-90014 Oulu, Finland. Electronic address: andre.juffer@oulu.fi.
authors.forename: André H
authors.initials: AH
authors.lastname: Juffer
mesh_terms: D008024:Ligands; D011506:Proteins / Q000378:metabolism*
chemical_list: D008024:Ligands; D011506:Proteins
keywords: FAD; NAD; Sequence-independent; Structural alignment; Structural similarity; TM-SITE