title: Reducing docking score variations arising from input differences.
abstract: The variability of docking results as a function of variations in ligand input conformations was studied for the GOLD, Glide, FlexX, and Surflex programs. It is concluded that there are two major effects leading to such variability: the adequacy of conformational search during docking and random "chaotic" effects arising from sensitivity to small input perturbations. It is shown that although the former is generally the stronger effect, the latter is also highly significant for almost all docking engines. The strong target-to-target variation of the magnitude of these effects is emphasized. The performance of different packages is compared using these measures. Guidelines are provided for different programs to reduce variability and improve reproducibility, which involve using a small number of input conformations as starting points for docking, followed by the selection of the top scoring docked pose from the results as the best docked solution.
authors.affiliation: Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto Medical Discovery Tower, Toronto, ON, M5G 1L7, Canada. mfeher@uhnres.utoronto.ca
authors.forename: Miklos
authors.initials: M
authors.lastname: Feher
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Williams
mesh_terms: D008024:Ligands; D008968:Molecular Conformation
chemical_list: D008024:Ligands