#!/usr/bin/env python # (C) 2022 Cadence Design Systems, Inc. (Cadence) # All rights reserved. # TERMS FOR USE OF SAMPLE CODE The software below ("Sample Code") is # provided to current licensees or subscribers of Cadence products or # SaaS offerings (each a "Customer"). # Customer is hereby permitted to use, copy, and modify the Sample Code, # subject to these terms. Cadence claims no rights to Customer's # modifications. Modification of Sample Code is at Customer's sole and # exclusive risk. Sample Code may require Customer to have a then # current license or subscription to the applicable Cadence offering. # THE SAMPLE CODE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, # EXPRESS OR IMPLIED. OPENEYE DISCLAIMS ALL WARRANTIES, INCLUDING, BUT # NOT LIMITED TO, WARRANTIES OF MERCHANTABILITY, FITNESS FOR A # PARTICULAR PURPOSE AND NONINFRINGEMENT. In no event shall Cadence be # liable for any damages or liability in connection with the Sample Code # or its use. ''' This script prepares an MD or docking-ready design unit with receptor from an input PDB or mmCIF file. Input parameters: Required: -in: The input PDB or mmCIF file -site_residue: Defines a binding site residue for pocket detection (Required for apo structures only) Optional: -map: Input mtz file containing the electron density map -loop_db: Input loop_db file for loop modeling -generate_tautomers: generate and use tautomers in the hydrogen network optimization -prefix: String to prepend to all output DU files -metadata: Input metadata JSON file -allow_filter_error: Run spruce prep even when structure fails spruce filter -verbose: boolean flag to trigger verbose logging Usage examples: python spruce_prep.py -in 3fly.cif python spruce_prep.py -in 3fly.pdb -metadata 3fly_metadata.json -generate_tautomers false python spruce_prep.py -in 3fly.pdb -map 3fly.mtz -verbose true -prefix 3FLY -loop_db my_loop_db.loop_db python spruce_prep.py -3p2q.pdb -site_residue 'HIS: 76: :A' ''' import sys from openeye import oechem from openeye import oegrid from openeye import oespruce from openeye import oedocking InterfaceData = ''' !PARAMETER -in !TYPE string !REQUIRED true !BRIEF Input PDB/CIF file name !END !PARAMETER -site_residue !TYPE string !REQUIRED false !BRIEF Site residue specification to indentify binding site (ex: 'HIS:42: :A') !END !PARAMETER -prefix !TYPE string !REQUIRED false !BRIEF prefix to append to all output DU file names !END !PARAMETER -map !TYPE string !REQUIRED false !LEGAL_VALUE *.mtz !BRIEF Input electron density file !END !PARAMETER -loop_db !TYPE string !REQUIRED false !LEGAL_VALUE *.loop_db !BRIEF Input database for loop modeling !END !PARAMETER -generate_tautomers !TYPE bool !REQUIRED false !DEFAULT true !BRIEF Option to generate and use tautomers in the hydrogen network optimization (optional) !END !PARAMETER -metadata !TYPE string !REQUIRED false !LEGAL_VALUE *.json !BRIEF Input structure metadata json file !END !PARAMETER -allow_filter_error !TYPE bool !REQUIRED false !DEFAULT false !BRIEF Option to allow running spruce prep even when structure fails spruce filter. !END !PARAMETER -verbose !TYPE bool !REQUIRED false !DEFAULT false !BRIEF Boolean flag to trigger verbose logging !END ''' def main(argv=sys.argv): itf = oechem.OEInterface(InterfaceData, argv) # read input parameters ifile = itf.GetString('-in') include_ed = False if itf.HasString('-map'): mapfile = itf.GetString('-map') include_ed = True include_loop = False if itf.HasString('-loopdb'): loopfile = itf.GetString('-loopdb') include_loop = True site_residue_specified = False if itf.HasString('-site_residue'): site_residue = itf.GetString('-site_residue') site_residue_specified = True has_prefix = False if itf.HasString('-prefix'): prefix = itf.GetString('-prefix') has_prefix = True if itf.GetBool('-verbose'): oechem.OEThrow.SetLevel(oechem.OEErrorLevel_Verbose) has_metadata = False if itf.HasString('-metadata'): metadata_json_name = itf.GetString('-metadata') with open(metadata_json_name, "r") as f: metadata_json = f.read() has_metadata = True allow_filter_error = itf.GetBool('-allow_filter_error') generate_tautomers = itf.GetBool('-generate_tautomers') # read PDB or CIF input file ifs = oechem.oemolistream() if not ifs.open(ifile): oechem.OEThrow.Fatal(f'Unable to open {ifile} for reading') if ifs.GetFormat() not in [oechem.OEFormat_PDB, oechem.OEFormat_CIF]: oechem.OEThrow.Fatal('Input file must be .pdb or .cif') ifs.SetFlavor(oechem.OEFormat_PDB, oechem.OEIFlavor_PDB_Default | oechem.OEIFlavor_PDB_DATA | oechem.OEIFlavor_PDB_ALTLOC) mol = oechem.OEGraphMol() if not oechem.OEReadMolecule(ifs, mol): oechem.OEThrow.Fatal(f'Unable to read molecule from {ifile}') # read mtz file if included ed = oegrid.OESkewGrid() if include_ed: if not oegrid.OEReadMTZ(mapfile, ed, oegrid.OEMTZMapType_Fwt): oechem.OEThrow.Fatal(f'Unable to read electron density file {mapfile}') makedu_opts = oespruce.OEMakeDesignUnitOptions() makedu_opts.GetSplitOptions().SetAlternateLocationHandling(oespruce.OEAlternateLocationOption_Combinatorial) makedu_opts.GetSplitOptions().SetMinLigAtoms(8) makedu_opts.GetSplitOptions().SetMaxLigAtoms(200) makedu_opts.GetSplitOptions().SetMaxLigResidues(20) makedu_opts.GetPrepOptions().GetEnumerateSitesOptions().SetEnumerateCofactorSites(False) makedu_opts.GetPrepOptions().GetEnumerateSitesOptions().SetCollapseNonSiteAlts(False) # read metadata file if provided metadata = oespruce.OEStructureMetadata() if has_metadata: oespruce.OEStructureMetadataFromJson(metadata, metadata_json) # set loop database if included if include_loop: makedu_opts.GetPrepOptions().GetBuildOptions().GetLoopBuilderOptions().SetLoopDBFilename(loopfile) # set tautomer generation flag makedu_opts.GetPrepOptions().GetProtonateOptions().SetGenerateTautomers(generate_tautomers) # run Spruce filter filter_opts = oespruce.OESpruceFilterOptions() filter = oespruce.OESpruceFilter(filter_opts, makedu_opts) ret_filter = filter.StandardizeAndFilter(mol, ed, metadata) if ret_filter !=oespruce.OESpruceFilterIssueCodes_Success: oechem.OEThrow.Warning(f'This structure fails spruce filter due to: ') oechem.OEThrow.Warning(filter.GetMessages()) if not allow_filter_error: oechem.OEThrow.Fatal('This structure fails spruce filter') # make the DUs if site_residue_specified: # use site residue if include_ed: design_units = oespruce.OEMakeDesignUnits(mol, ed, metadata, makedu_opts, site_residue) else: design_units = oespruce.OEMakeDesignUnits(mol, metadata, makedu_opts, site_residue) else: # assume structure has bound ligand if include_ed: design_units = oespruce.OEMakeDesignUnits(mol, ed, metadata, makedu_opts) else: design_units = oespruce.OEMakeDesignUnits(mol, metadata, makedu_opts) # validate the DUs validator = oespruce.OEValidateDesignUnit() for i, design_unit in enumerate(design_units): ret_validator = validator.Validate(design_unit, metadata) if ret_validator != oespruce.OEDesignUnitIssueCodes_Success: oechem.OEThrow.Warning(f'Design unit {design_unit.GetTitle()} did not pass the DU validator.') oechem.OEThrow.Warning(validator.GetMessages()) # make the receptor ropts = oedocking.OEMakeReceptorOptions() if not oedocking.OEMakeReceptor(design_unit, ropts): oechem.OEThrow.Warning(f'Unable to generate receptor for design unit {design_unit.GetTitle()}') # write the DU print(design_unit.GetTitle()) basename = f'{design_unit.GetTitle()}'.replace('(', '_').replace(')', '_').replace(' > ', 'DU_').replace(' ', '_').replace('/', '-')[:-1] if has_prefix: ofile = f'{prefix}_{basename}.oedu' else: ofile = f'{basename}.oedu' if not oechem.OEWriteDesignUnit(ofile, design_unit): oechem.OEThrow.Warning(f'Unable to write design unit {design_unit.GetTitle()}') if __name__ == "__main__": sys.exit(main(sys.argv))