title: Optimization of multiple-sequence alignment based on multiple-structure alignment.
abstract: Routinely used multiple-sequence alignment methods use only sequence information. Consequently, they may produce inaccurate alignments. Multiple-structure alignment methods, on the other hand, optimize structural alignment by ignoring sequence information. Here, we present an optimization method that unifies sequence and structure information. The alignment score is based on standard amino acid substitution probabilities combined with newly computed three-dimensional structure alignment probabilities. The advantage of our alignment scheme is in its ability to produce more accurate multiple alignments. We demonstrate the usefulness of the method in three applications: 1) computing more accurate multiple-sequence alignments, 2) analyzing protein conformational changes, and 3) computation of amino acid structure-sequence conservation with application to protein-protein docking prediction. The method is available at http://bioinfo3d.cs.tau.ac.il/staccato/.
authors.affiliation: School of Computer Science, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, Israel. maxshats@cs.tau.ac.il
authors.forename: Maxim
authors.initials: M
authors.lastname: Shatsky
authors.forename: Ruth
authors.initials: R
authors.lastname: Nussinov
authors.forename: Haim J
authors.initials: HJ
authors.lastname: Wolfson
mesh_terms: D000595:Amino Acid Sequence; D017124:Conserved Sequence; D019143:Evolution, Molecular; D005982:Glutathione Transferase / Q000737:chemistry; D008962:Models, Theoretical; D008969:Molecular Sequence Data; D011506:Proteins / Q000737:chemistry*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D011506:Proteins; D005982:Glutathione Transferase