title: Numerical errors and chaotic behavior in docking simulations.
abstract: This work examines the sensitivity of docking programs to tiny changes in ligand input files. The results show that nearly identical ligand input structures can produce dramatically different top-scoring docked poses. Even changing the atom order in a ligand input file can produce significantly different poses and scores. In well-behaved cases the docking variations are small and follow a normal distribution around a central pose and score, but in many cases the variations are large and reflect wildly different top scores and binding modes. The docking variations are characterized by statistical methods, and the sensitivity of high-throughput and more precise docking methods are compared. The results demonstrate that part of docking variation is due to numerical sensitivity and potentially chaotic effects in current docking algorithms and not solely due to incomplete ligand conformation and pose searching. These results have major implications for the way docking is currently used for pose prediction, ranking, and virtual screening.
authors.affiliation: Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto Medical Discovery Tower, 101 College Street, Suite 5-361, 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; D008958:Models, Molecular; D017711:Nonlinear Dynamics; D011485:Protein Binding; D011487:Protein Conformation; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism; D012107:Research Design
chemical_list: D008024:Ligands; D011494:Protein Kinases