In –> out simulation

Introduction

The unbinding simulation aims to find the unbinding path of a small molecule to a given receptor. It explores the dissociative path of a molecule and is useful when studying the dissociative binding path, or to open up the pocket Our software will automatically set the center of the simulation box along an exit simulation. 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

Modes

  • in_out

  • in_out_soft

Recommendations

  1. We recommend using at least 30 CPUs.

  2. Expected computational time is 2h.

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: 'complex.pdb'
chain: 'Z' # Ligand chain ID
resname: 'STR' # Ligand residue name
# Distance to track along the simulation
atom_dist:
- "A:2:HG" # First atom (chain ID:residue number:atom name
- "A:3:CA" # Second atom
in_out: true
cpus: 30

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