Out –> in simulation

Introduction

The binding simulation aims to find the binding path of a small molecule to a given receptor. Our software will automatically place the ligand around the specified initial site and build the simulation box based on the coordinates of the final_site. Upon completion of the simulation, the user will be presented with a ranking of binding modes of the small molecule.

Input

  • protein-ligand PDB file

  • YAML file with parameters

Default parameters

  • iterations: 100

  • pele steps: 8

Recommendations

  1. We recommend using at least 50 CPUs.

  2. Expected computational time is 6h.

1. Complex Preparation

Prepare the system with Maestro (Protein Preparation Wizard) and output as complex.pdb.

2. Input 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
# Distance to track along the simulation
atom_dist:
- "A:2:CA" # First atom (chain ID:residue number:atom name)
- "B:3:CG" # Second atom
cpus: 60
out_in: true
initial_site: "A:577:N"
final_site: "A:867:CB"

Note: PELE will automatically . Then simulation will start.

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