Creating apo OEDesignUnits from a PDB file

Preparation of a biological structure file (PDB, mmCIF) to a fully charged, hydrogenated, molecular componentized object (design unit; DU; OEDesignUnit) is one of the more advanced functionalities offered through Spruce TK. This example shows how to construct apo DUs using an input PDB file and the OEMakeDesignUnits function.

Command Line Interface

This example uses an input PDB file, and will output a set of DUs from it to a temporary directory (see OEMakeDesignUnits for details on the API).

make_apo_design_units <input biomolecular PDB> <site_residue> [<electron density mtz>] <LoopModelingTemplateDB>]

Code

Download code

make_apo_design_units.py and both the 1w50.pdb (the input PDB file), 1w50.mtz (the input MTZ file), and spruce_bace.loop_db (the input loopDB file)

#!/usr/bin/env python
# (C) 2022 Cadence Design Systems, Inc. (Cadence) 
# All rights reserved.
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# subject to these terms. Cadence claims no rights to Customer's
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# NOT LIMITED TO, WARRANTIES OF MERCHANTABILITY, FITNESS FOR A
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# or its use.

#############################################################################
# Script to prepare proteins into design units
#############################################################################
import sys
import os
from openeye import oechem
from openeye import oegrid
from openeye import oespruce


def main(argv=sys.argv):

    if len(argv) < 3 or len(argv) > 5:
        oechem.OEThrow.Usage(
            "%s <infile> <site_residue> [<mtzfile>] [<loopdbfile>]" % argv[0]
        )

    ifs = oechem.oemolistream()
    ifile = argv[1]
    if not ifs.open(ifile):
        oechem.OEThrow.Fatal("Unable to open %s for reading" % ifile)

    site_residue = argv[2]

    include_loop = False
    include_ed = False
    if len(argv) > 3:
        if len(argv) == 5 or (len(argv) == 4 and "mtz" in argv[3]):
            edfile = argv[3]
            ed = oegrid.OESkewGrid()
            if not oegrid.OEReadMTZ(edfile, ed, oegrid.OEMTZMapType_Fwt):
                oechem.OEThrow.Fatal(
                    "Unable to read electron density file %s" % edfile
                )  # noqa
            include_ed = True
        if len(argv) == 5:
            loopfile = argv[4]
            include_loop = True
        elif len(argv) == 4 and "mtz" not in argv[3]:
            loopfile = argv[3]
            include_loop = True

    if ifs.GetFormat() not in [oechem.OEFormat_PDB, oechem.OEFormat_CIF]:
        oechem.OEThrow.Fatal("Only works for .pdb or .cif input files")

    ifs.SetFlavor(oechem.OEFormat_PDB, oechem.OEIFlavor_PDB_SpruceDefault)
    ifs.SetFlavor(oechem.OEFormat_MMCIF, oechem.OEIFlavor_MMCIF_SpruceDefault)

    mol = oechem.OEGraphMol()
    if not oechem.OEReadMolecule(ifs, mol):
        oechem.OEThrow.Fatal("Unable to read molecule from %s" % ifile)

    metadata = oespruce.OEStructureMetadata()
    opts = oespruce.OEMakeDesignUnitOptions()
    opts.GetPrepOptions().GetBuildOptions().GetLoopBuilderOptions().SetBuildTails(False)
    if include_loop:
        opts.GetPrepOptions().GetBuildOptions().GetLoopBuilderOptions().SetLoopDBFilename(
            loopfile
        )

    if include_ed:
        design_units = oespruce.OEMakeDesignUnits(mol, ed, metadata, opts, site_residue)
    else:
        design_units = oespruce.OEMakeDesignUnits(mol, metadata, opts, site_residue)

    base_name = os.path.basename(ifile)[:-4] + "_DU_{}.oedu"
    for i, design_unit in enumerate(design_units):
        oechem.OEWriteDesignUnit(base_name.format(i), design_unit)


if __name__ == "__main__":
    sys.exit(main(sys.argv))

Example

make_apo_design_units.py 1w50.pdb "ASP:228: :A" 1w50.mtz  spruce_bace.loop_db

will generate the following output (failing to add partial charges to iodine):

DPI: 0.13, RFree: 0.28, Resolution: 1.75
Processing BU # 0 with title: BETA-SECRETASE 1, chains A
Found gap between ALA 157   A 1   and ALA 168   A 1  , with sequence GFPLNQSEVL
Opened database spruce_bace.loop_db
LoopDatabase Info:
    276 loops from RSCB last synced on 03-19-2020, were added to LoopTemplateDatabase on 03-19-2020 using Spruce Toolkit 1.0.0.a
    The loop database was built with a max loop length of 22, a termini crop length of 2, and excluding regular secondary structures
Warning: Failed to charge miscellaneous components
Warning: Unable to add partial charges and radii to DesignUnit: BETA-SECRETASE 1(A)__DU__biounit
Iridium Category: NA, DPI: 0.13, RFree: 0.28, Resolution: 1.75