make-ligand-mol2¶

pestifer make-ligand-mol2 generates Tripos mol2 files for every HETATM ligand in a PDB whose residue name is not already defined in the loaded CHARMM topologies. Each mol2 is ready to feed directly to the CGenFF binary or to the CGenFF web tool at https://cgenff.com/ for atom typing and parameter generation.

For each unknown ligand the subcommand:

Reads the heavy-atom coordinates and atom names from the input PDB.
Fetches the ligand’s SMILES from the RCSB Chemical Component Dictionary (data.rcsb.org), preferring the OpenEye canonical-stereo form.
Builds an RDKit Mol whose heavy atoms are in the original PDB order and carry the original PDB atom names.
Protonates the ligand at the target pH (default 7.4) using Dimorphite-DL, which is aware of multi-pKa groups such as phosphates.
Adds explicit hydrogens with 3D coordinates and writes a Tripos mol2 via Open Babel. The mol2’s @<TRIPOS>MOLECULE title is set to the residue name so that the CGenFF binary/web tool registers the resulting RESI under that exact name.

Heavy-atom names from the input PDB are preserved into the mol2, which means the .str file generated by CGenFF can later be remapped back to the original PDB naming without ambiguity.

Requirements¶

The subcommand uses three optional dependencies:

The rdkit and dimorphite_dl Python packages. Install them together with pestifer via the optional extra:
```
pip install 'pestifer[ligand-paramgen]'
```
Or, in a conda environment:
```
conda install -c conda-forge rdkit
pip install dimorphite_dl
```
The obabel binary from Open Babel must be on $PATH. On most Linux distributions this is in an openbabel (or similar) package.

For help with pestifer make-ligand-mol2:

$ pestifer make-ligand-mol2 --help

Examples¶

Generate mol2 files for every non-CHARMM ligand in PDB 1HPV:

$ pestifer make-ligand-mol2 1HPV --outdir mol2_out

The output for that PDB looks like:

=== make-ligand-mol2 summary (outdir: mol2_out) ===
Already in CHARMM (1): HOH

Generated 1 mol2 file(s):
    478  ->  mol2_out/478.mol2

The input source can also be a local PDB file:

$ pestifer make-ligand-mol2 ./my_structure.pdb --outdir mol2_out

If the RCSB Data API has no entry for a particular ligand (or the default SMILES is unsuitable, e.g. you want a different tautomer), you can supply a SMILES override:

$ pestifer make-ligand-mol2 1IEP --smiles STI='Cc1ccc(NC(=O)c2ccc(cc2)CN2CCN(CC2)C)cc1Nc1nccc(n1)-c1cccnc1'

The --smiles flag can be repeated for multiple residues.

The protonation pH can be adjusted with --ph:

$ pestifer make-ligand-mol2 1AKE --ph 7.0

Per-ligand failures (no RCSB SMILES, RDKit cannot sanitize the structure, obabel fails, etc.) are reported in the summary but do not abort the run, so a single problematic ligand will not block mol2 generation for the rest.

CGenFF round-trip¶

The recommended workflow once a mol2 file has been generated:

Upload the mol2 to https://cgenff.com/ (free academic license) and download the resulting .str.
Drop the .str into ~/.pestifer/toppar/ – the per-user custom CHARMM cache. Any pestifer build that subsequently encounters that residue will resolve it automatically, without requiring charmmff.user_custom entries in the input YAML.

See user_custom for details on the user-custom search-path machinery.