dimorphite-ojmb 1.2.5.post1

An open-source program for enumerating the ionization states of drug-like small molecules

Dimorphite-DL

This repository is a modified version of Durrant Lab's original Dimorphite-DL implementation (original article).

Changes were brought to facilitate its installation and integration in bigger cheminformatics projects (see CHANGES.md).

What is it?

As stated on Durrant's Lab original GitLab page:

Dimorphite-DL adds hydrogen atoms to molecular representations, as appropriate for a user-specified pH range. It is a fast, accurate, accessible, and modular open-source program for enumerating small-molecule ionization states. Users can provide SMILES strings from the command line or via an .smi file.

Citation

If you use Dimorphite-DL in your research, please cite:

Ropp PJ, Kaminsky JC, Yablonski S, Durrant JD (2019) Dimorphite-DL: An open-source program for enumerating the ionization states of drug-like small molecules. J Cheminform 11:14. doi:10.1186/s13321-019-0336-9.

Licensing

Dimorphite-DL is released under the Apache 2.0 license. See LICENCE.txt for details.

Installation

This modified version of Dimorphite-DL can be installed using pip:

pip install dimorphite-ojmb

If the above does not work, you can run the installation like so:

python -m pip install dimorphite-ojmb

Usage

usage: dimorphite [-h] [--min_ph MIN] [--max_ph MAX] [--pka_precision PRE]
                  [--smiles SMI] [--smiles_file FILE] [--output_file FILE]
                  [--max_variants MXV] [--label_states] [--silent] [--test]

Dimorphite 1.2.4: Creates models of appropriately protonated small moleucles.
Apache 2.0 License. Copyright 2020 Jacob D. Durrant.

Options:
  -h, --help           Show this message and exit.
  --min_ph MIN         minimum pH to consider (default: 6.4)
  --max_ph MAX         maximum pH to consider (default: 8.4)
  --pka_precision PRE  pKa precision factor (number of standard devations,
                       default: 1.0)
  --smiles SMI         SMILES string to protonate NOTE: This argument is
                       mutually exclusive with smiles_file.  [required]
  --smiles_file FILE   file that contains SMILES strings to protonate NOTE:
                       This argument is mutually exclusive with smiles.
                       [required]
  --output_file FILE   output file to write protonated SMILES (optional)
  --max_variants MXV   limit number of variants per input compound (default:
                       128)
  --label_states       label protonated SMILES with target state (i.e.,
                       "DEPROTONATED", "PROTONATED", or "BOTH").
  --silent             do not print any messages to the screen
  --test               run unit tests (for debugging)

The default pH range is 6.4 to 8.4, considered biologically relevant pH.

CLI usage examples

  dimorphite --smiles_file sample_molecules.smi
  dimorphite --smiles "CCC(=O)O" --min_ph -3.0 --max_ph -2.0
  dimorphite --smiles "CCCN" --min_ph -3.0 --max_ph -2.0 --output_file output.smi
  dimorphite --smiles_file sample_molecules.smi --pka_precision 2.0 --label_states
  dimorphite --test

Advanced Usage

It is also possible to access Dimorphite-DL from another Python script, rather than from the command line. Here's an example:

from rdkit import Chem
import dimorphite_dl

# Using the dimorphite_dl.run() function, you can run Dimorphite-DL exactly as
# you would from the command line. Here's an example:
dimorphite_dl.run(smiles="CCCN",
                  min_ph=-3.0,
                  max_ph=-2.0)


# One can also provide multiple SMILES at once.
dimorphite_dl.run(["C[C@](F)(Br)CC(O)=O", "CCCCCN"],
                  min_ph=5.0,
                  max_ph=9.0,
                  silent=True)

Caveats

Dimorphite-DL deprotonates indoles and pyrroles around pH 14.5. But these substructures can also be protonated around pH -3.5. Dimorphite does not perform the protonation.

Authors and Contacts

See the CONTRIBUTORS.md file for a full list of contributors. Please contact Jacob Durrant ([e-mail]) with any questions.