Enhancing systematic protein-protein docking methods using ray casting: Application to ATTRACT

Abstract : Systematic protein–protein docking methods need to evaluate a huge number of different probe configurations, thus leading to high computational cost. We present an efficient filter—ray casting filter (RCF)—that enables a notable speed‐up of systematic protein–protein docking. The high efficiency of RCF is the outcome of the following factors: (i) extracting of pockets and protrusions on the surfaces of the proteins using visibilities; (ii) a ray casting method that finds aligned receptor pocket/probe protrusion pairs without explicit similarity computations. The RCF method enables the integration of systematic methods and local shape feature matching methods. To verify the efficiency and the accuracy of RCF, we integrated it with a systematic protein–protein docking approach (ATTRACT) based on a reduced protein representation. The test results show that the integrated docking approach is much faster. At the same time, it ranks the lowest ligand root‐mean‐square deviation (RMSD) (L_rms) solutions higher when docking enzyme–enzyme inhibitor complexes. Consequently, RCF not only enables much faster execution of systematic docking runs but also improves the qualities of docking predictions.