title: TASSER: an automated method for the prediction of protein tertiary structures in CASP6.
abstract: The recently developed TASSER (Threading/ASSembly/Refinement) method is applied to predict the tertiary structures of all CASP6 targets. TASSER is a hierarchical approach that consists of template identification by the threading program PROSPECTOR_3, followed by tertiary structure assembly via rearranging continuous template fragments. Assembly occurs using parallel hyperbolic Monte Carlo sampling under the guide of an optimized, reduced force field that includes knowledge-based statistical potentials and spatial restraints extracted from threading alignments. Models are automatically selected from the Monte Carlo trajectories in the low-temperature replicas using the clustering program SPICKER. For all 90 CASP targets/domains, PROSPECTOR_3 generates initial alignments with an average root-mean-square deviation (RMSD) to native of 8.4 A with 79% coverage. After TASSER reassembly, the average RMSD decreases to 5.4 A over the same aligned residues; the overall cumulative TM-score increases from 39.44 to 52.53. Despite significant improvements over the PROSPECTOR_3 template alignment observed in all target categories, the overall quality of the final models is essentially dictated by the quality of threading templates: The average TM-scores of TASSER models in the three categories are, respectively, 0.79 [comparative modeling (CM), 43 targets/domains], 0.47 [fold recognition (FR), 37 targets/domains], and 0.30 [new fold (NF), 10 targets/domains]. This highlights the need to develop novel (or improved) approaches to identify very distant targets as well as better NF algorithms.
authors.affiliation: Center of Excellence in Bioinformatics, University at Buffalo, Buffalo, New York.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Center of Excellence in Bioinformatics, University at Buffalo, Buffalo, New York.
authors.forename: Adrian K
authors.initials: AK
authors.lastname: Arakaki
authors.affiliation: Center of Excellence in Bioinformatics, University at Buffalo, Buffalo, New York.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Skolnick
mesh_terms: D000465:Algorithms; D001331:Automation; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D003201:Computers; D003627:Data Interpretation, Statistical; D030562:Databases, Protein; D008958:Models, Molecular; D009010:Monte Carlo Method; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D016415:Sequence Alignment; D012984:Software