g748e-PosePredictionProtocol.txt

Name

HADDOCK2.2 protein-ligand protocol

Software

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

System Preparation Parameters

Assumed pH neutral
Protein charges from OPLS force field
Ligand parameters and charges from PRODRG

System Preparation Method

The bound receptor was used, including SO4, DMS (if present) and crystallographic water molecules. 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.

Pose Prediction Parameters

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

Pose Prediction Method

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 removing solutions with positive scores (indicative of clashed) originating from the superimposition procedure used to create the starting models. The receptor and all crystallographic waters, SO4 and DMS (if present) were kept rigid during the refinement.

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.
The score does include in this case also the protein-ligand water energies for all waters within 3.5A of both the protein and the ligand.

Answer 1

Yes

Answer 2

Yes