title: An iterative structure-assisted approach to sequence alignment and comparative modeling.
abstract: Correct alignment of the sequence of a target protein with those of homologues of known three-dimensional structure is a key step in comparative modeling. Usually an iterative approach that takes account of the local and overall structural features is required. We describe such an approach that exploits databases of structural alignments of homologous proteins (HOMSTRAD, http:/(/)www-cryst.bioc.cam.ac.uk/ approximately homstrad) and protein superfamilies (CAMPASS, http:/(/)www-cryst.bioc.cam.ac.uk/ approximately campass), in which structure-based alignments are analyzed and formatted with the program JOY (http:/(/)www-cryst.bioc.cam.ac.uk/ approximately joy) to reveal conserved local structural features. The databases facilitate the recognition of a family or superfamily, they assist in the selection of useful parent structures, they are helpful in alignment of the target sequences with the parent set, and are useful for deriving relationships that can be used in validating models. In the iterative approach, a model is constructed on the basis of the proposed sequence alignment and this is then reexpressed in the JOY format and realigned with the parent set. This is repeated until the model and sequence alignment is optimized. We examine the case for comparison and use of multiple structures of family members, rather than a single parent structure. We use the targets attempted by our group in CASP3 to assess the value of such procedures.
authors.affiliation: Department of Biochemistry, University of Cambridge, United Kingdom.
authors.forename: D F
authors.initials: DF
authors.lastname: Burke
authors.forename: C M
authors.initials: CM
authors.lastname: Deane
authors.forename: H A
authors.initials: HA
authors.lastname: Nagarajaram
authors.forename: N
authors.initials: N
authors.lastname: Campillo
authors.forename: M
authors.initials: M
authors.lastname: Martin-Martinez
authors.forename: J
authors.initials: J
authors.lastname: Mendes
authors.forename: F
authors.initials: F
authors.lastname: Molina
authors.forename: J
authors.initials: J
authors.lastname: Perry
authors.forename: B V
authors.initials: BV
authors.lastname: Reddy
authors.forename: C M
authors.initials: CM
authors.lastname: Soares
authors.forename: R E
authors.initials: RE
authors.lastname: Steward
authors.forename: M
authors.initials: M
authors.lastname: Williams
authors.forename: M A
authors.initials: MA
authors.lastname: Carrondo
authors.forename: T L
authors.initials: TL
authors.lastname: Blundell
authors.forename: K
authors.initials: K
authors.lastname: Mizuguchi
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D019992:Databases as Topic; D020407:Internet; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018272:Porins / Q000737:chemistry; D011506:Proteins / Q000737:chemistry*; D012260:Ribonucleases / Q000737:chemistry; D016415:Sequence Alignment
chemical_list: D018272:Porins; D011506:Proteins; D012260:Ribonucleases