Comparative study of several algorithms for flexible ligand docking.

We have performed a comparative assessment of several programs for flexible molecular docking: DOCK 4.0, FlexX 1.8, AutoDock 3.0, GOLD 1.2 and ICM 2.8. This was accomplished using two different studies: docking experiments on a data set of 37 protein-ligand complexes and screening a library containing 10,037 entries against 11 different proteins. The docking accuracy of the methods was judged based on the corresponding rank-one solutions. We have found that the fraction of molecules docked with acceptable accuracy is 0.47, 0.31, 0.35, 0.52 and 0.93 for, respectively, AutoDock, DOCK, FlexX, GOLD and ICM. Thus ICM provided the highest accuracy in ligand docking against these receptors. The results from the other programs are found to be less accurate and of approximately the same quality. A speed comparison demonstrated that FlexX was the fastest and AutoDock was the slowest among the tested docking programs. The database screening was performed using DOCK, FlexX and ICM. ICM was able to identify the original ligands within the top 1% of the total library in 17 cases. The corresponding number for DOCK and FlexX was 7 and 8, respectively. We have estimated that in virtual database screening, 50% of the potentially active compounds will be found among approximately 1.5% of the top scoring solutions found with ICM and among approximately 9% of the top scoring solutions produced by DOCK and FlexX.