PSI-DOCK: Towards highly efficient and accurate flexible ligand docking

• Published in: Proteins, structure, function, and bioinformatics structure, function, and bioinformatics, 2006-03, Vol.62 (4), p.934-946
• Main Authors: Pei, Jianfeng, Wang, Qi, Liu, Zhenming, Li, Qingliang, Yang, Kun, Lai, Luhua
• Format: Article
• Language: English
• Subjects: Algorithms; Binding Sites; docking; docking, SCORE 3.0; drug design; Entropy; Ligands; message passing interface (MPI); Metals; Proteins - chemistry; PSI-DOCK; Reproducibility of Results; SCORE 3.0; scoring; Thermodynamics; virtual screening
• ISSN: 0887-3585; 1097-0134
• DOI: 10.1002/prot.20790

We have developed a new docking method, Pose‐Sensitive Inclined (PSI)‐DOCK, for flexible ligand docking. An improved SCORE function has been developed and used in PSI‐DOCK for binding free energy evaluation. The improved SCORE function was able to reproduce the absolute binding free energies of a training set of 200 protein–ligand complexes with a correlation coefficient of 0.788 and a standard error of 8.13 kJ/mol. For ligand binding pose exploration, a unique searching strategy was designed in PSI‐DOCK. In the first step, a tabu‐enhanced genetic algorithm with a rapid shape‐complementary scoring function is used to roughly explore and store potential binding poses of the ligand. Then, these predicted binding poses are optimized and compete against each other by using a genetic algorithm with the accurate SCORE function to determine the binding pose with the lowest docking energy. The PSI‐DOCK 1.0 program is highly efficient in identifying the experimental binding pose. For a test dataset of 194 complexes, PSI‐DOCK 1.0 achieved a 67% success rate (RMSD