Basic ligand preparation

Basic ligand preparation#

Command line script#

Upon installing Meeko, mk_prepare_ligand.py is available in the terminal and running it should print a help message. This script writes one or more PDBQT files for AutoDock-GPU or AutoDock-Vina. It reads SD files, often referred to as SDF, and these can contain multiple molecules. The input molecules must have all hydrogens as real atoms, and 3D positions. Mol2 files are supported, but the SDF is strongly preferred.

To print the help message pass the -h option:

mk_prepare_ligand.py -h

Writing a single PDBQT file:

mk_prepare_ligand.py -i molecule.sdf -o molecule.pdbqt

If the -o option is omitted, the output filename will be the same as the input but with .pdbqt extension. Option - prints the PDBQT string to standard output instead of writing to a file.

Writing multiple PDBQT files from an SD file with multiple molecules:

mk_prepare_ligand.py -i multi_mol.sdf --multimol_outdir folder_for_pdbqt_files

Optionally, passing -z or --multimol_targz will compress the output as .tar.gz files with 10000 PDBQT files each.

Python API#

The following script reads a file named molecules.sdf using RDKit, configures an instance of MoleculePreparation with default options, and creates PDBQT strings for all molecules in the input file:

from meeko import MoleculePreparation
from meeko import PDBQTWriterLegacy
from rdkit import Chem

input_filename = "molecules.sdf"

# iterate over molecules in SD file
for mol in Chem.SDMolSupplier(input_filename, removeHs=False):
    mk_prep = MoleculePreparation()
    molsetup_list = mk_prep(mol)

    molsetup = molsetup_list[0]

    pdbqt_string = PDBQTWriterLegacy.write_string(molsetup)

The pdbqt_string can be written to a file for docking with AutoDock-GPU or AutoDock-Vina, or passed directly to Vina within Python using Vina’s Python API, and avoiding writing PDBQT files to the filesystem.

Note that calling mk_prep returns a list of molecule setups. As of v0.6.0, this list contains only one element unless mk_prep is configured for reactive docking, which is not the case in this example. This is why we are considering the first (and only) molecule setup in the list.

Reading Precomputed Charges#

Meeko supports reading partial charges directly from MOL2 files when using the Tripos charge format via the atom property _TriposPartialCharge using RDKit’s Chem.MolFromMol2File. The basic usage is as follows:

mk_prepare_ligand.py -i ligand.mol2 --charge_model read

Additionally, it is possible to read precomputed charges that are assigned to atoms in the RDKit molecule object from a named property, not limited to _TriposPartialCharge. See the following Python API example:

from meeko import MoleculePreparation
from meeko import PDBQTWriterLegacy
from rdkit import Chem

input_filename = "path_to_liagand.mol2"
output_filename = "path_to_liagand.pdbqt"
mol = Chem.MolFromMol2File(input_filename, removeHs=False)
mk_prep = MoleculePreparation(charge_model="read", charge_atom_prop="_TriposPartialCharge")
# or alternatively, compute and assign a named atom property and do:
# mk_prep = MoleculePreparation(charge_model="read", charge_atom_prop="my_charge_property")
molsetup_list = mk_prep(mol)
molsetup = molsetup_list[0]
pdbqt_string = PDBQTWriterLegacy.write_string(molsetup)

with open(output_filename, "w") as f:
    f.write(pdbqt_string[0])

This option ensures that existing charges are retained (til the merging of hydrogens) instead of recalculating them. It may be useful for reading precomputed charges from other software, such as AmberTools, OpenEye or Schrodinger.

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