title: Retrieving backbone string neighbors provides insights into structural modeling of membrane proteins.
abstract: Identification of protein structural neighbors to a query is fundamental in structure and function prediction. Here we present BS-align, a systematic method to retrieve backbone string neighbors from primary sequences as templates for protein modeling. The backbone conformation of a protein is represented by the backbone string, as defined in Ramachandran space. The backbone string of a query can be accurately predicted by two innovative technologies: a knowledge-driven sequence alignment and encoding of a backbone string element profile. Then, the predicted backbone string is employed to align against a backbone string database and retrieve a set of backbone string neighbors. The backbone string neighbors were shown to be close to native structures of query proteins. BS-align was successfully employed to predict models of 10 membrane proteins with lengths ranging between 229 and 595 residues, and whose high-resolution structural determinations were difficult to elucidate both by experiment and prediction. The obtained TM-scores and root mean square deviations of the models confirmed that the models based on the backbone string neighbors retrieved by the BS-align were very close to the native membrane structures although the query and the neighbor shared a very low sequence identity. The backbone string system represents a new road for the prediction of protein structure from sequence, and suggests that the similarity of the backbone string would be more informative than describing a protein as belonging to a fold.
authors.affiliation: Department of Chemistry, Tongji University, 1239 Siping Road, Shanghai 200092, China.
authors.forename: Jiang-Ming
authors.initials: JM
authors.lastname: Sun
authors.forename: Tong-Hua
authors.initials: TH
authors.lastname: Li
authors.forename: Pei-Sheng
authors.initials: PS
authors.lastname: Cong
authors.forename: Sheng-Nan
authors.initials: SN
authors.lastname: Tang
authors.forename: Wen-Wei
authors.initials: WW
authors.lastname: Xiong
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011513:Proteus mirabilis; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein
chemical_list: D008565:Membrane Proteins