title: Evaluation of docking/scoring approaches: a comparative study based on MMP3 inhibitors.
abstract: An increasing number of docking/scoring programs are available that use different sampling and scoring algorithms. A reliable scoring function is the crucial element of such approaches. Comparative studies are needed to evaluate their current capabilities. DOCK4 with force field and PMF scoring as well as FlexX were used to evaluate the predictive power of these docking/scoring approaches to identify the correct binding mode of 61 MMP-3 inhibitors in a crystal structure of stromelysin and also to rank them according to their different binding affinities. It was found that DOCK4/PMF scoring performs significantly better than FlexX and DOCK4/FF in both ranking ligands and predicting their binding modes. Most notably, DOCK4/PMF was the only scoring/docking approach that found a significant correlation between binding affinity and predicted score of the docked inhibitors. However, comparing only those cases where the correct binding mode was identified (scoring highest among sampled poses), FlexX showed the best 'fine tuning' (lowest rmsd) in predicted binding modes. The results suggest that not so much the sampling procedure but rather the scoring function is the crucial element of a docking program.
authors.affiliation: Bayer Research Center, West Haven, CT 06516, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ha
authors.forename: R
authors.initials: R
authors.lastname: Andreani
authors.forename: A
authors.initials: A
authors.lastname: Robbins
authors.forename: I
authors.initials: I
authors.lastname: Muegge
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D019278:Matrix Metalloproteinase 3 / Q000737:chemistry; D061965:Matrix Metalloproteinase Inhibitors; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D012984:Software
chemical_list: D008024:Ligands; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D019278:Matrix Metalloproteinase 3