HADDOCK2.2 protein-ligand protocol
HADDOCK Webserver 2.2
OpenEye Omega 2017.6.1
OpenEye Shape 2017.6.1
OpenEye ROCS 3.2.2.2
ChemmineR 2.26
fmcsR 1.16
Assumed pH neutral
Protein charges from OPLS force field
Ligand parameters and charges from PRODRG
Templates were identified using the advanced search functionality of the RCSB PDB and the following settings: 70% sequence identity and presence of a ligand. No further processing or modelling was performed on the 36 templates that were identified. A single receptor was used for the docking of each target ligand. The selection of the template for the docking was based on the similarity of the crystallographic ligand to the competition ligand as calculated by the MCS tanimoto index between every template ligand and the full competition set. The ligands were converted from SMILES format to 3D structures using OE-Omega and sampling up to 500 conformers per ligand. We selected 10 poses for docking based on the tanimoto-combo (shape + colour) similarity between the generated ligand poses and the selected (see above) template ligand. The selected ligand conformers were superimposed on the respective crystallographic ligands using the shape overlay functionality of the OE-Shape Toolkit.
Default HADDOCK2.2 server setting except for the following changes
randomization of starting orientations turned off
rigid body energy minimization turned off
delenph = False
initiosteps = 0
cool1_steps = 0
cool2_steps = 0
cool3_steps = 0
w_vdw_0 = 1.0
w_elec_2 = 0.1
number of models for all stages = 200
RMSD clustering with a 2A cutoff
The docking was performed using the HADDOCK2.2 web server (van Zundert et al. J. Mol. Biol. 2015) using default parameters except for those specified above. Ensembles of 10 ligand structures and a single receptor were provided as input for ensemble refinement.
The poses selected for submission are representative structures of the clusters identified during the analysis of the structures produced during the it-water stage of HADDOCK after inspection to remove clashing solutions originating from the superimposition procedure used to create the starting models.
The scoring function used for ranking the poses is the standard HADDOCK score for the explicit solvent (water) refinement (It-water) which is defined as: HADDOCK-score = 1.0*Evdw + 0.1*Eelec + 1.0*Edesol, Edesol an empirical desolvation energy term (Fernandez-Recio et al. J. Mol. Biol. 2004). The intermolecular energies are calculated using the OPLS united atom force field parameters (Jorgensen, W. L. & Tirado-Rives. J. Am. Chem. Soc. 1988) for non-bonded atoms, using a 8.5 angstrom cut-off with a shifting function for the electrostatic energy and switching function between 6.5 and 8.5 angstrom for the van der Waals energy. For the electrostatics energy, a dielectric constant of 10 is used.
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