Example repo for setting up ligand RBFE simulations.
For theory, have a look at this paper
This tutorial is based on the BioSimSpace Tutorials
1. Install mamba here (preferred) or condahere
2. Create a clean environment:
conda create -n obss
3. Install BioSimSpace:
conda activate obss
mamba install -c openbiosim biosimspace
- Make sure Amber is installed.
You can install Amber here
- Starting structures
- Start with a prepared protein (or other target) system:
- Choose a good-quality starting structure (ideally with at least one ligand bound pose),
- Determine the protonation states of amino acid side chains,
- Fix missing residues/chains
- And determine the protonation states of your ligands.
- For a ligand series, it's best to start from the coordinates of a single bound pose of a ligand to which all the other ligands are aligned
- Decide if you want to include protein terminal residues, and how you deal with co-factors such as metals. You can use meze to parameterise zinc-metalloenzymes.
- Directory structure
The data in this tutorial is structured as:
data/
|---- inputs/
| |---- ligands/
| | |---- ligand_1.sdf Input ligand SDF file for ligand 1
| | |---- ligand_2.sdf Input ligand SDF file for ligand 2
| |---- protein/
| | |---- kpc2.prepared.pdb Prepared protein PDB file
It's recommended you follow the same structure.
- Parameterisation
If you have any non-standard residues or ligands, it's recommended that you use e.g. leap in ambertools for parameterisation. You can then load in the topology (prmtop/prm7) and coordinate (inpcrd/rst7) files to BioSimSpace.
BioSimSpace uses GROMACS for solvation by default, so if you want to solvate your systems with Amber you can do so at the parameterisation step.
You can create the perturbation network with the Jupyter notebook 01_setup_network.ipynb.
This will create three more folders in the inputs directory:
data/
|---- inputs/
| |---- ligands/
| | |---- ligand_1.sdf Input ligand SDF file for ligand 1
| | |---- ligand_2.sdf Input ligand SDF file for ligand 2
| | |---- images/ Directory created by lomap
| | | |---- network.png Image of the network
| | |---- inputs/ Directory created by lomap
| | | |---- 000_ligand_1.sdf Input files processed by lomap
| | |---- outputs/ Directory created by lomap
| | | |---- network.csv Network saved a csv file
| | | |---- lomap_score_with_connection.txt Lomap output
| | | |---- lomap.pickle Lomap output
| | | |---- lomap.txt Lomap output
| |---- protein/
| | |---- kpc2.prepared.pdb Prepared protein PDB file