Multi-target Docking using Autodock Vina
AutoDock Vina 1.1.2/MGL Tools 1.5.6/Open Babel 2.3.0/UCSF Chimera 1.11.1/Raccoon 1.0/H++ server/Modeler Web Server
Assumed pH 7.4
MMFF94 force field for geometry optimization for the ligands.
Gasteiger charges
1. The ligands were protonated using OpenBabel 2.3.0 at pH 7.4.
2. MMFF94 force field was used to generate the best conformer (out of 500) of each ligand using 'obconformer' module of Open Babel and write it to a optimized ligand conformation file (for each ligand) after 100 steps of geometry optimization.
3. Docking was performed using several sets of protein coordinates from the PDB, namely:
1OSH, 3DCT, 3DCU, 3FLI, 3FXV, 3HC5, 3HC6, 3L1B, 3OKH, 3OLF, 3OMK, 3OMM, 3OOF, 3P88, 3RUT, 4QE6, 4QE8, and the "apo" structure provided in the D3R package.
All the mutations in the PDB conformations were switched back to that of the "apo" structure in order to make all protein sequences identical. The missing residues in the proteins (if any) were added using Modeller web server integrated with UCSF Chimera. Incomplete sidechains were added using Dunbrack rotamer library integrated with Dock Prep module of UCSF Chimera. A 300 steps energy minimzation with 'steepest descent' algorithm was followed by 100 steps of energy minimization using 'conjugate gradients' was performed to remove sidechain clashes.
4. The protonation state of the amino acid residues in the protein were adjusted according to pH 7.4.
5. The GRID parameters for respective protein conformations are mentioned below:
Number of points: x = 15, y = 15, z = 15
Spacing = 1.000 Angstrom
Centre of Grid for the various systems:
1OSH: x = 4.196, y = 28.838, z = 54.346
3DCT: x = 138.14, y = 26.838, z =78.903
3DCU: x = 12.942, y = 18.722, z = 39.186
3FLI: x = 40.971, y = 2.003, z = -13.316
3FXV: x = -14.979, y = 53.966, z = 1.574
3HC5: x = 0.555, y = 26.274, z = 59.037
3HC6: x = 131.785, y = 138.014, z = 79.299
3OKH: x = 12.526, y = 61.252, z = 15.17
3OLF: x = 13.49, y = 21.945, z = 4.314
3OMK: x = 22.205, y = 19.405, z = 4.794
3OMM: x = 13.378, y = 21.851, z = 4.322
3OOF: x = 19.597, y = 11.984, z = 50.808
3P88: x = 92.483, y = 38.611, z = 139.097
3RUT: x = -0.777, y = 52.606, z = -20.983
3RUU: x = 26.34, y = -0.854, z = -20.422
4QE6: x = 10.865, y = -14.799, z = 12.28
4QE8: x = -9.687, y = -3.997, z = 17.437
Apo: x = 42.365, y = 12.380, z = 4.683
6. All protein and ligand structures were transformed into .pdbqt format using Raccoon.
Iterated Local Search global optimizer search method
Exhaustiveness=8
Vina scoring function (empirical + knowledge-based function)
Molecular docking was performed using Autodock Vina with above mentioned parameters. All docking poses for a given ligand (up to 9 poses for each protein structure) were sorted according to free energy of binding, and duplicate poses were removed by looking at the RMSD between poses after aligning the C-alpha atoms (a cutoff of 2 Angstrom was used). Note that the final set of 5 ranked poses may well include poses docked into different protein structures, thus the files do not always have the same prefix. The energy provided in the final mol file is the prediction from Autodock Vina.