title: Improving protein structure prediction using multiple sequence-based contact predictions.
abstract: Although residue-residue contact maps dictate the topology of proteins, sequence-based ab initio contact predictions have been found little use in actual structure prediction due to the low accuracy. We developed a composite set of nine SVM-based contact predictors that are used in I-TASSER simulation in combination with sparse template contact restraints. When testing the strategy on 273 nonhomologous targets, remarkable improvements of I-TASSER models were observed for both easy and hard targets, with p value by Student's t test<0.00001 and 0.001, respectively. In several cases, template modeling score increases by >30%, which essentially converts "nonfoldable" targets into "foldable" ones. In CASP9, I-TASSER employed ab initio contact predictions, and generated models for 26 FM targets with a GDT-score 16% and 44% higher than the second and third best servers from other groups, respectively. These findings demonstrate a new avenue to improve the accuracy of protein structure prediction especially for free-modeling targets.
authors.affiliation: Center for Bioinformatics and Department of Molecular Bioscience, University of Kansas, Lawrence, KS 66047, USA.
authors.forename: Sitao
authors.initials: S
authors.lastname: Wu
authors.forename: Andras
authors.initials: A
authors.lastname: Szilagyi
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry; D053181:Caspase 8 / Q000737:chemistry; D053453:Caspase 9 / Q000737:chemistry; D003198:Computer Simulation; D004268:DNA-Binding Proteins / Q000737:chemistry; D008958:Models, Molecular; D011487:Protein Conformation; D060388:Support Vector Machine; D014157:Transcription Factors / Q000737:chemistry; D014764:Viral Proteins / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C067996:MotA protein, Enterobacteria phage T4; D014157:Transcription Factors; D014764:Viral Proteins; D053181:Caspase 8; D053453:Caspase 9