Prepare your own Pocket Exploration

To prepare your own pocket exploration to obtain putative binding sites of your small molecule and retrieve the most promising binding modes of yout ligand, please follow the steps below.

Article: https://nostrumbiodiscovery.github.io/papers/Software/index.html#ppi-pele-monte-carlo-simulations-using-pele-to-identify-a-proteinprotein-inhibitor-binding-site-and-pose

Input (further explained below):

  • Protein-ligand.pdb

Output (further explained below):

  • Most promising pockets ranked

  • Most promising binding modes ranked

Computational time: 24h

1. Complex Preparation

Prepare the system with maestro (Protein Preparation Wizard) and output a complex.pdb. The complex.pdb must contain protein-ligand. The ligand can be place anywhere as it will be automatically placed all around the protein by our automatic pipeline.

Make sure the ligand has:

  • Unique chain

  • No atomnames with spaces or single letter

  • Any residuename except UNK

2. Input Preparation

Prepare the input file input.yml:

Pocket Exploration (24h)

system: 'docking2grid6n4b_thc.pdb'
chain: 'L'
resname: 'THC'
seed: 12345
#Distance to track along the simulation
atom_dist:
- "A:2:CA" #First atom to make the distance to
- "B:3:CG" #Second atom to make the distance to
allosteric: true

For more optional flags please refer to optative falgs

3. Run simulation

To run the system launch the simulation with the next command:

python -m pele_platform.main input.yml

4. Output

Best pockets ranked by ligand energy:

working_folder/refinement_simulation/results/clusters

Best snapshots ranked by ligand energy:

working_folder/refinement_simulation/results/BestStructs/