1146-1-y050b-PosePredictionProtocol.txt

Name

Flexible-ligand/ensemble receptor docking protocol

Software

Smina (A fork of Autodock Vina) / RDKit (Version 2018.03.2) / PDB2PQR (Version 2.1.1) / AutoDockTools (Version 1.5.6)

System Preparation Parameters

Assumed pH 4.5
Gasteiger charges

System Preparation Method

1. Receptor conformation selection for docking:
Search for the available BACE-1 structures in PDB database, and then select the ligand-bound receptor structures by ligand similarity with the predicted ligands.
5 receptor structures (PDB_id: 3DV5, 3K5C, 4DPF, 4DPI, 4GMI) were selected for ensemble receptors docking.

2. Receptor preparation: PDB2PQR was used to add hydrogens to the receptor structures (—-ph_calc-method=propka —with-ph=4.5),
AutoDockTools was used to convert the input receptors files to pdbqt format and assign Gasteiger charges.


3. Ligand Conformation selection for docking:
Ligand conformational libraries were generated using RDkit (maximum 1000 conformers per ligand, ETKDG method).
Ligand conformers within 5 kcal/mol from the lowest energy were selected for docking. (Energy calculation of ligand conformers using MMFF94)

Pose Prediction Parameters

Ligands were treated as flexible, receptor structures were treated as rigid.
The docking box site were determined by the known crystal ligands. (Known crystal ligand is used for autobox)
Exhaustiveness=32
Num_modes=20
Energy_range=7
Standard Vina scoring function

Pose Prediction Method

Docking runs were executed with the above specified parameters while default values were applied for the rest of the variables. The final predicted pose from the Smina docking are submitted with this protocol.

Answer 1

Yes

Answer 2

Yes