SP⁵: Improving protein fold recognition by using torsion angle profiles and profile-based gap penalty model

How to organize the structural fold of a protein is one of the challenges in protein structure prediction.We have developed a series of single (non-consensus) methods (SPARKS, SP², SP³, SP⁴) that are based on weighted matching of two to four sequence and structure-based profiles. There is a robust improvement of the accuracy and sensitivity of fold recognition as the number of matching profiles increases. Here, we introduced a new profile-profile comparison term based on real-value dihedral torsion angles. Together with updated real-value solvent accessibility profile and a new variable gap-penalty model based on fractional power of insertion/deletion profiles, the new method (SP⁵) leads to a robust improvement over previous SP method. There is a 2% absolute increase (5% relative improvement) in alignment accuracy over SP⁴ based on two independent benchmarks. Moreover, SP⁵ makes 7% absolute increase (22% relative improvement) in success rate of recognizing correct structural folds, and 32% relative improvement in model accuracy of models within the same fold in lindahl benchmarks. In addition, modeling accuracy of top 1 ranked models is improved by 12% over SP⁴ for the difficult targets in CASP 7 test set. These results highlight the importance of harnessing predicted structural properties in challenging remote-homolog recognition. The SP⁵ server is available at http://sparks.informatics.iupui.edu.