Effects of initial settings on computational protein–ligand docking accuracies for several docking programs

Abstract

In this study, the influences of initial settings, i.e. initial conformations, configurations and docking parameters, on docking results were investigated. The conformations used in the study were generated by the CAMDAS program. After the conformational search calculations, five structures were selected from the conformer groups according to their conformation energies and root mean square deviations against crystal structures; for example, the lowest energy conformer, as well as the closest and farthest conformers to the crystal structure, was retrieved. Several docking parameter settings were used (default, high speed, generating 50 poses). In this study, docking calculations were conducted using the GOLD, eHiTS, AutoDock, AutoDock vina, FRED and DOCK programs. The success rates of GOLD, eHiTS and FRED were better than those of AutoDock, AutoDock vina and DOCK. The docking results using the farthest conformations were worse than those obtained using other conformations, indicating that some conformation search for the ligand molecule should be performed before the docking calculations.

Keywords::

• protein–ligand docking
• pose selection
• ligand conformation
• configuration

Acknowledgements

This work was supported by a grant-in-aid for scientific research [23790137] from the Japan Society for the Promotion of Science.