Tutorial

Take one protein-ligand complex (PDB_id: 1eby) as an example.

1. Preparation

Download Lin_F9
Initial files of 1eby_ligand.mol2 and 1eby_protein.pdb are obtained from PDBbind database
MGLTools are used for preparing PDBQT files: 1eby_ligand.pdbqt and 1eby_protein.pdbqt

http://mgltools.scripps.edu/downloads

DockRMSD is used for the calculation of RMSD between docking pose and original crystal pose of the same ligand molecule

https://zhanglab.ccmb.med.umich.edu/DockRMSD/

2. Local optimization

Perform local optimization of crystal ligand pose

./smina.static -r 1eby_protein.pdbqt -l 1eby_ligand.pdbqt --local_only --scoring Lin_F9 -o 1eby_optimized.pdb

Print the score of locally optimized pose

grep 'Affinity' 1eby_optimized.pdb | awk '{print $3}'

3. Flexible re-docking

Perform flexible ligand docking using native ligand conformation and native protein conformation

./smina.static -r 1eby_protein.pdbqt -l 1eby_ligand.pdbqt --autobox_ligand 1eby_ligand.pdbqt --scoring Lin_F9 -o 1eby_flexRedock.pdb

Print the score of the best-scored pose

grep -m1 'Affinity' 1eby_flexRedock.pdb | awk '{print $3}'

Calculate the RMSD between the best-scored pose and crystal ligand pose

python split_docked.py 1eby_flexRedock.pdb 1eby_flexRedock
./calc_rmsd_for_pose.sh 1eby_flexRedock/1eby_flexRedock_01.pdb 1eby_ligand.mol2

4. End-to-end (E2E) docking

E2E docking protocol combines ligand conformer generation and flexible docking

4.1. OpenBabel 2.4.1 used to generate maximum 10 conformers per ligand.

babel -imol2 1eby_ligand.mol2 -osdf 1eby_ligand_2D.sdf --gen2D
babel -isdf 1eby_ligand_2D.sdf -osdf 1eby_ligand_3D.sdf --gen3D
obabel 1eby_ligand_3D.sdf -O conformers.sdf --conformer --nconf 10 --score rmsd --writeconformers

4.2. All conformers are sequentially docked to protein receptor structure using flexible docking.

python split_sdf.py conformers.sdf 1eby_conformers
/E2E_docking.sh

Print the score of the best-scored pose

grep -m1 'Affinity' 1eby_E2E/*.pdb | sort -nk3 | head -n 1 | awk '{print $3}'

Calculate the RMSD between the best-scored pose and crystal ligand pose

./GetSplit.sh
./calc_rmsd_for_pose.sh 1eby_E2E_top1.pdb 1eby_ligand.mol2