PoseButcher 0.0.18

A tool for categorising and segmenting virtual hits with reference to experimental protein structures and (fragment) hits.

PoseButcher

"A good butcher always trims the fat"

PoseButcher is a tool for categorising and segmenting virtual hits with reference to experimental protein structures and (fragment) hits.

Ligand atoms are tagged with categories:

- GOOD:

	* fragment space: within the fragment bolus
	* pocket X: in a specified catalytic/allosteric pocket X

- BAD:
	
	* protein clash: Clashing with the protein
	* solvent space: Heading out of the protein/crystal

Usage at a glance

1. Create the butcher (see PoseButcher.__init__):

	from posebutcher import PoseButcher
	butcher = PoseButcher(protein, hits, pockets)

2. Chop up a posed virtual hit (rdkit.ROMol with a conformer):

	result = butcher.chop(mol)

3. Tag a compound based on its pocket occupancy and clashes:

	tags = butcher.tag(mol)

4. Explore the expansion opportunities from a given atom in a virtual hit

	result = butcher.explore(mol)

5. (Coming soon) Trim a parts of a compound that clash with a protein or leave the crystal

	mol = butcher.trim(mol)

6. (Coming soon) Score how well a virtual hit recapitulates shape and colour of the fragment bolus

	score: float = butcher.score(mol)

Sample output

Protein, ligand, and catalytic site pockets with Open3D:

A chopped up ligand:

Exploring expansion vector into a desirable pocket

Installation

1. Install PoseButcher:

pip install --upgrade posebutcher

N.B. open3d version 0.18 or greater is required

Common installation issues

PyGAMer build fails on Linux HPC

PoseButcher uses PyGAMer to calculate the surface meshes from PDB files (used for the protein and fragment bolus). The current workaround is to install PoseButcher without PyGAMer and then import an existing PoseButcher using PoseButcher.from_directory or PoseButcher.protein_mesh = '/path/to/protein_mesh.ply'.

pip install --upgrade MolParse open3d jupyterlab pandas
pip install --upgrade --no-dependencies posebutcher

If initialised without the from_directory method, add a protein mesh to an existing PoseButcher using:

butcher.protein_mesh = '/path/to/protein_mesh.ply'
butcher._clip_pockets()

Examples

PoseButcher ships with some open access test data from the XChem group at Diamond Light Source, funded by the ASAP consortium.

To run the "example.ipynb":

git clone [e-mail]:mwinokan/PoseButcher
cd PoseButcher
jupyter lab