Protein minimization¶

Introduction¶

The package to minimize the energy of the system by slightly perturbing the protein and the ligand to optimize all interactions.

Inputs¶

protein-ligand complex PDB file

YAML file with parameters

Default parameters¶

iterations: 20

pele_steps: 12

constraint level: 2

Recommendations¶

Expected computational time is ~30 mins.

1. Complex Preparation¶

Prepare the system consisting of protein and docked ligand with Schrödinger Protein Preparation Wizard. We would usually recommend protonating the protein (mandatory), deleting water molecules and ions as well as filling in missing loops and side chains.

Make sure the ligand has:

unique chain ID

unique PDB atom names with no spaces or single letters

any residue name except for UNK

2. Input file preparation¶

Prepare the input file input.yml:

system: 'docking2grid6n4b_thc.pdb' # Protein-ligand PDB
chain: 'L' # Ligand chain ID
resname: 'THC' # Ligand residue name
seed: 12345
cpus: 20
rescoring: true # Minimize

For more optional flags please refer to optional flags.

3. Run simulation¶

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

python -m pele_platform.main input.yml

4. Output¶

Raw output¶

Trajectory and report files for each simulation are located in working_folder/output. That’s where you can find detailed information on each snapshot (PDB file, binding energy, metrics, etc.).

Selected poses¶

Clusters¶

Upon completion of the simulation, all trajectories are clustered based on ligand heavy atom coordinates. Then, a cluster representative with the best binding energy (or metric of your choice) is selected. Ranked cluster representatives can be found in:

working_folder/results/clusters

Best snapshots¶

In addition, top 100 structures with the best binding energy (or metric of your choice) are retrieved. This is done to ensure the clustering algorithm did not skip any valuable results. They are stored in:

working_folder/results/top_poses