Single‐body residue‐level knowledge‐based energy score combined with sequence‐profile and secondary structure information for fold recognition

An elaborate knowledge-based energy function is designed for fold recognition. It is a residue-level single-body potential so that highly efficient dynamic programming method can be used for alignment optimization. It contains a backbone torsion term, a buried surface term, and a contact-energy term. The energy score combined with sequence profile and secondary structure information leads to an algorithm called SPARKS (Sequence, secondary structure Profiles and Residue-level Knowledge-based energy Score) for fold recognition. Compared with the popular PSI-BLAST, SPARKS is 21% more accurate in sequence-sequence alignment in ProSup benchmark and 10%, 25%, and 20% more sensitive in detecting the family, superfamily, fold similarities in the Lindahl benchmark, respectively. Moreover, it is one of the best methods for sensitivity (the number of correctly recognized proteins), alignment accuracy (based on the MaxSub score), and specificity (the average number of correctly recognized proteins whose scores are higher than the first false positives) in LiveBench 7 among more than twenty servers of non-consensus methods. The simple algorithm used in SPARKS has the potential for further improvement. This highly efficient method can be used for fold recognition on genomic scales. A web server is established for academic users on http://theory.med.buffalo.edu.