Fold recognition by combining sequence profiles derived from evolution and from depth-dependent structural alignment of fragments.
Recognizing structural similarity without significant sequence identity has proved to be a challenging task. Sequence-based and structure-based methods as well as their combinations have been developed. Here, we propose a fold-recognition method that incorporates structural information without the need of sequence-to-structure threading. This is accomplished by generating sequence profiles from protein structural fragments. The structure-derived sequence profiles allow a simple integration with evolution-derived sequence profiles and secondary-structural information for an optimized alignment by efficient dynamic programming. The resulting method (called SP(3)) is found to make a statistically significant improvement in both sensitivity of fold recognition and accuracy of alignment over the method based on evolution-derived sequence profiles alone (SP) and the method based on evolution-derived sequence profile and secondary structure profile (SP(2)). SP(3) was tested in SALIGN benchmark for alignment accuracy and Lindahl, PROSPECTOR 3.0, and LiveBench 8.0 benchmarks for remote-homology detection and model accuracy. SP(3) is found to be the most sensitive and accurate single-method server in all benchmarks tested where other methods are available for comparison (although its results are statistically indistinguishable from the next best in some cases and the comparison is subjected to the limitation of time-dependent sequence and/or structural library used by different methods.). In LiveBench 8.0, its accuracy rivals some of the consensus methods such as ShotGun-INBGU, Pmodeller3, Pcons4, and ROBETTA. SP(3) fold-recognition server is available on http://theory.med.buffalo.edu.
Zhou
Hongyi
H
Howard Hughes Medical Institute Center for Single Molecule Biophysics, Department of Physiology & Biophysics, State University of New York at Buffalo, 14214, USA.
Zhou
Yaoqi
Y
D000465:Algorithms; D000595:Amino Acid Sequence; D005075:Biological Evolution; D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D019143:Evolution, Molecular; D015233:Models, Statistical; D019151:Peptide Library; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012680:Sensitivity and Specificity; D016415:Sequence Alignment / Q000379:methods*; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid; D012984:Software; D013997:Time Factors
D019151:Peptide Library