title: The Performance of Several Docking Programs at Reproducing Protein-Macrolide-Like Crystal Structures.
abstract: The accuracy of five docking programs at reproducing crystallographic structures of complexes of 8 macrolides and 12 related macrocyclic structures, all with their corresponding receptors, was evaluated. Self-docking calculations indicated excellent performance in all cases (mean RMSD values ≤ 1.0) and confirmed the speed of AutoDock Vina. Afterwards, the lowest-energy conformer of each molecule and all the conformers lying 0-10 kcal/mol above it (as given by Macrocycle, from MacroModel 10.0) were subjected to standard docking calculations. While each docking method has its own merits, the observed speed of the programs was as follows: Glide 6.6 > AutoDock Vina 1.1.2 > DOCK 6.5 >> AutoDock 4.2.6 > AutoDock 3.0.5. For most of the complexes, the five methods predicted quite correct poses of ligands at the binding sites, but the lower RMSD values for the poses of highest affinity were in the order: Glide 6.6 ≈ AutoDock Vina ≈ DOCK 6.5 > AutoDock 4.2.6 >> AutoDock 3.0.5. By choosing the poses closest to the crystal structure the order was: AutoDock Vina > Glide 6.6 ≈ DOCK 6.5 ≥ AutoDock 4.2.6 >> AutoDock 3.0.5. Re-scoring (AutoDock 4.2.6//AutoDock Vina, Amber Score and MM-GBSA) improved the agreement between the calculated and experimental data. For all intents and purposes, these three methods are equally reliable.
authors.affiliation: Organic Chemistry Section, Facultat de Química, Diagonal 645, Universitat de Barcelona, 08028 Barcelona, Catalonia, Spain. alecastro@ub.edu.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Castro-Alvarez
authors.affiliation: Organic Chemistry Section, Facultat de Química, Diagonal 645, Universitat de Barcelona, 08028 Barcelona, Catalonia, Spain. amcosta@ub.edu.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Costa
authors.affiliation: Organic Chemistry Section, Facultat de Química, Diagonal 645, Universitat de Barcelona, 08028 Barcelona, Catalonia, Spain. jvilarrasa@ub.edu.
authors.forename: Jaume
authors.initials: J
authors.lastname: Vilarrasa
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D008024:Ligands; D047028:Macrocyclic Compounds / Q000737:chemistry; D018942:Macrolides / Q000737:chemistry*; D062105:Molecular Docking Simulation / Q000379:methods*; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry*; D012984:Software
chemical_list: D008024:Ligands; D047028:Macrocyclic Compounds; D018942:Macrolides; D011506:Proteins
keywords: AutoDock; DOCK; Glide; Vina; docking; macrolides; natural products