How good are state-of-the-art docking tools in predicting ligand binding modes in protein-protein interfaces?
Protein-protein interfaces (PPIs) are an important class of drug targets. We report on the first large-scale validation study on docking into PPIs. DrugScore-adapted AutoDock3 and Glide showed good success rates with a moderate drop-off compared to docking to "classical targets". An analysis of the binding energetics in a PPI allows identifying those interfaces that are amenable for docking. The results are important for deciding if structure-based design approaches can be applied to a particular PPI.
Institute of Pharmaceutical and Medicinal Chemistry, Department of Mathematics and Natural Sciences, Heinrich-Heine-University, Universitätsstr.1, 40225 Düsseldorf, Germany.
Dennis M
DM
Krüger
Gisela
G
Jessen
Holger
H
Gohlke
D000465:Algorithms; D000818:Animals; D001665:Binding Sites; D015195:Drug Design; D006801:Humans; D007700:Kinetics; D008024:Ligands; D062105:Molecular Docking Simulation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011506:Proteins / Q000737:chemistry*; D012984:Software; D013816:Thermodynamics
D008024:Ligands; D011506:Proteins