Bioisostere Examples

The following table lists the currently available Bioisostere TK examples:

Program	Description
database	Building Brood Database (CHOMP)
query	Creating Brood Query
hitlist	Generating Brood Hits
matches	Generating Brood Matches
fragment_overlay	Overlay between Fragments
replace_fragment	Replacing a Fragment in a Molecule
cpddb	Building and Using an External Compound Database
cluster	Clustering Brood Hits
2molLinker_query	Creating a Brood Query by Linking Two Molecules (Bridging)
combo_builder	Building Combined Hits from Different Queries of the Same Molecule
score_hitlist	Curating Scored Fragment Hits with OEScoreHitlist
connection_mol_builder	Comparing Connection and Molecule Building Outcomes

Building Brood Database (CHOMP)

The following code example shows how to build a Brood database from a library of molecules.

This example demonstrates end-to-end fragment database construction, including fragment generation, optional filtering, and writing the final Brood database.

See also

• OEFragmentOptions class

• OEDBScreenOptions class

• OEDBBuilder class

• OEDBWriter class

• OEGenerateConformers function

Listing 1: Building Brood Database (CHOMP)

/*
 (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.
 */
#include <cstdio>
#include <string>
#include <openeye.h>

#include <oeplatform.h>
#include <oesystem.h>
#include <oechem.h>
#include <oebioisostere.h>
#include <oemolprop.h>


class ChompOptions : public OESystem::OEOptions
{
public:
  ChompOptions(std::string name = "ChompOptions")
    :OESystem::OEOptions(name)
  {
    OESystem::OEStringParameter pDBName("-out");
    pDBName.SetRequired(true);
    pDBName.SetKeyless(2);
    pDBName.SetVisibility(OESystem::OEParamVisibility::Simple);
    pDBName.SetBrief("Output database folder name");
    m_dbParam = AddParameter(pDBName);
    
    m_FragmentOptions = static_cast<OEBioisostere::OEFragmentOptions*>(AddOption(OEBioisostere::OEFragmentOptions()));
    m_ScreenOptions = static_cast<OEBioisostere::OEDBScreenOptions*>(AddOption(OEBioisostere::OEDBScreenOptions()));
  }
  
  ChompOptions(const ChompOptions&) = default;
  ChompOptions& operator=(const ChompOptions&) = default;
  ~ChompOptions() override =default;
  ChompOptions* CreateCopy() const override { return new ChompOptions(*this);}
  
  std::string GetDBName() const { return m_dbParam->GetStringValue(); }
  OEBioisostere::OEFragmentOptions* GetFragOpts() const { return m_FragmentOptions; }
  OEBioisostere::OEDBScreenOptions* GetScreenOpts() const { return m_ScreenOptions; }

private:
  OESystem::OEParameter* m_dbParam;
  OEBioisostere::OEFragmentOptions* m_FragmentOptions;
  OEBioisostere::OEDBScreenOptions* m_ScreenOptions;
};


int main(int argc, char* argv[])
{
  ChompOptions chompOpts;
  OEChem::OESimpleAppOptions opts(chompOpts, "BroodDataBase", OEChem::OEFileStringType::Mol);
  
  if (OESystem::OEConfigureOpts(opts, argc, argv, false) == OESystem::OEOptsConfigureStatus::Help)
    return 0;
  chompOpts.UpdateValues(opts);
  
  OEChem::oemolistream ifs;
  if (!ifs.open(opts.GetInFile()))
    OESystem::OEThrow.Fatal("Unable to open %s for reading", opts.GetInFile().c_str());
  
  printf("Generating fragments...\n");
  OEBioisostere::OEDBBuilder builder = OEBioisostere::OEDBBuilder( *chompOpts.GetFragOpts());
  OEChem::OEGraphMol mol;
  while(OEChem::OEReadMolecule(ifs, mol))
    builder.Generate(mol);
  
  printf("Building 2D fragments library...\n");
  builder.Filter(*OEBioisostere::OECreateFragFilter());
  builder.Expand(*OEBioisostere::OECreateFlipperOptions());
  builder.Screen(*chompOpts.GetScreenOpts());
  
  printf("Generating fragment conformers...\n");
  OEBioisostere::OEDBWriter writer;
  writer.Init(chompOpts.GetDBName());
  unsigned count=0;
  OESystem::OEIter<OEChem::OEMCMolBase> frag = builder.GetFrags();
  for(; frag; ++frag)
  {
    count++;
    OEBioisostere::OEGenerateConformers(*frag);
    writer.Write(*frag);
  }
  writer.Finish();
  printf("Generated fragments: %d \n",count);
}

Download code

brood_database.cpp

Creating Brood Query

The following code example shows how to create a Brood query from a molecule that could be used for bioisosteric fragment replacements using Brood.

See also

• OEBroodQuery class

• OECreateBroodQuery function

Listing 2: Creating Brood Query

/*
 (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.
 */
#include <cstdio>
#include <string>
#include <openeye.h>

#include <oeplatform.h>
#include <oesystem.h>
#include <oechem.h>
#include <oebioisostere.h>


class QueryOptions : public OESystem::OEOptions
{
public:
  QueryOptions(std::string name = "QueryOptions")
  :OESystem::OEOptions(name)
  {
    OESystem::OEUIntParameter idxParam("-atomIndices");
    idxParam.SetIsList(true);
    idxParam.SetRequired(true);
    idxParam.SetBrief("Index of atoms in fragment");
    m_idxParam = AddParameter(idxParam);
    
    OEChem::OEFileStringParameter duParam("-du",OEChem::OEFileStringType::DU);
    duParam.SetBrief("Design unit containg protein target for bump check");
    m_duParam = AddParameter(duParam);
    
    OESystem::OEUIntParameter maskParam("-proteinMask", OEBio::OEDesignUnitComponents::TargetComplexNoSolvent);
    maskParam.SetBrief("Design unit mask to identify protein target");
    m_maskParam = AddParameter(maskParam);
    
    OEChem::OEFileStringParameter selectDUParam("-selectDU",OEChem::OEFileStringType::DU);
    selectDUParam.SetBrief("Design unit containg select protein for bump check");
    m_selectDUParam = AddParameter(selectDUParam);
    
    OESystem::OEUIntParameter maskSelectParam("-proteinSelectMask", OEBio::OEDesignUnitComponents::TargetComplexNoSolvent);
    maskSelectParam.SetBrief("Design unit mask to identify select protein target");
    m_maskSelectParam = AddParameter(maskSelectParam);
  }
  
  QueryOptions(const QueryOptions&) = default;
  QueryOptions& operator=(const QueryOptions&) = default;
  ~QueryOptions() override =default;
  QueryOptions* CreateCopy() const override { return new QueryOptions(*this);}
  
  std::vector<int> GetIndices()
  {
    std::vector<int> indices;
    OESystem::OEIter<const std::string> Value = m_idxParam->GetStringValues();
    for (;Value;++Value)
    {
      indices.push_back(std::stoi(Value));
    }
    return indices;
  }
  
  bool GetDU(OEChem::OESimpleAppOptions opts, OEBio::OEDesignUnit& du)
  {
    OEPlatform::oeifstream ifs;
    if(!m_duParam->GetHasValue())
      return false;
    if(!ifs.open(m_duParam->GetStringValue()))
      OESystem::OEThrow.Fatal("Unable to open %s for reading", opts.GetInFile().c_str());

    if(!OEBio::OEReadDesignUnit(ifs, du))
      OESystem::OEThrow.Fatal("Unable to read design unit");
    return true;
  }
  
  int GetProteinMask()
  {
    if (m_maskParam->GetHasValue())
      return std::stoi(m_maskParam->GetStringValue());
    return std::stoi(m_maskParam->GetStringDefault());
  }

  bool GetSelectDU(OEChem::OESimpleAppOptions opts, OEBio::OEDesignUnit& selectDU)
  {
    OEPlatform::oeifstream ifs;
    if(!m_selectDUParam->GetHasValue())
      return false;
    if(!ifs.open(m_selectDUParam->GetStringValue()))
      OESystem::OEThrow.Fatal("Unable to open %s for reading", opts.GetInFile().c_str());
    
    if(!OEBio::OEReadDesignUnit(ifs, selectDU))
      OESystem::OEThrow.Fatal("Unable to read design unit");
    return true;
  }
  
  int GetSelectProteinMask()
  {
    if (m_maskSelectParam->GetHasValue())
      return std::stoi(m_maskSelectParam->GetStringValue());
    return std::stoi(m_maskSelectParam->GetStringDefault());
  }
private:
  OESystem::OEParameter* m_idxParam;
  OESystem::OEParameter* m_duParam;
  OESystem::OEParameter* m_maskParam;
  OESystem::OEParameter* m_selectDUParam;
  OESystem::OEParameter* m_maskSelectParam;
};

int main(int argc, char* argv[])
{
  QueryOptions queryOpts;
  OEChem::OESimpleAppOptions opts(queryOpts, "BroodQuery", OEChem::OEFileStringType::Mol3D, "oeb");
  
  if (OESystem::OEConfigureOpts(opts, argc, argv, false) == OESystem::OEOptsConfigureStatus::Help)
    return 0;
  queryOpts.UpdateValues(opts);
  
  OEChem::oemolistream ifs;
  if (!ifs.open(opts.GetInFile()))
    OESystem::OEThrow.Fatal("Unable to open %s for reading", opts.GetInFile().c_str());
  
  OEChem::oemolostream ofs;
  if (!ofs.open(opts.GetOutFile()))
    OESystem::OEThrow.Fatal("Unable to open %s for writing", opts.GetOutFile().c_str());
  
  OEChem::OEMol queryMol;
  if (!OEChem::OEReadMolecule(ifs,queryMol))
    OESystem::OEThrow.Fatal("Unable to load molecule");
  
  std::vector<int> indices = queryOpts.GetIndices();
  std::vector<OEChem::OEAtomBase*> atoms;
  for (const auto& idx:indices)
  {
    OEChem::OEAtomBase* atom;
    atom = queryMol.GetAtom(OEChem::OEHasAtomIdx(idx));
    if (atom == nullptr)
      OESystem::OEThrow.Fatal("Invalid atom index %d", idx);
    atoms.push_back(std::move(atom));
  }

  OEChem::OEAtomBondSet selection;
  selection.AddAtoms(atoms);
  
  OEBioisostere::OEBroodQuery query;
  OEBio::OEDesignUnit du;
  OEBio::OEDesignUnit selectDU;
  unsigned retCode;
  
  if (!queryOpts.GetDU(opts, du) && !queryOpts.GetSelectDU(opts, selectDU))
    retCode = OEBioisostere::OECreateBroodQuery(query, queryMol, selection);
  else if (!queryOpts.GetDU(opts, du) && queryOpts.GetSelectDU(opts, selectDU))
  {
    const bool passingProteinSelect = true;
    retCode = OEBioisostere::OECreateBroodQuery(query, queryMol, selection, selectDU, queryOpts.GetSelectProteinMask(), passingProteinSelect);
  }
  else if (!queryOpts.GetSelectDU(opts, selectDU))
    retCode = OEBioisostere::OECreateBroodQuery(query, queryMol, selection, du, queryOpts.GetProteinMask());
  else
    retCode = OEBioisostere::OECreateBroodQuery(query, queryMol, selection, du, queryOpts.GetProteinMask(), selectDU, queryOpts.GetSelectProteinMask());
  
  if(retCode != OEBioisostere::OEBroodStatusCode::Success)
    OESystem::OEThrow.Fatal("%s", OEBioisostere::OEGetBroodStatus(retCode).c_str());
  
  OEBioisostere::OEWriteBroodQuery(ofs, query);
}

Download code

brood_query.cpp

Generating Brood Hits

The following code example shows how to perform bioisosteric fragment replacements on a Brood query and generate a hit list.

See also

• OEBroodGeneralOptions class

• OEBroodScoreOptions class

• OEBroodHitlistOptions class

• OEBroodOverlay class

• OEHitlistBuilder class

Listing 3: Generating Brood Hits

/*
 (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.
 */
#include <cstdio>
#include <openeye.h>

#include <oeplatform.h>
#include <oesystem.h>
#include <oechem.h>
#include <oebioisostere.h>


class BroodOptions : public OESystem::OEOptions
{
public:
  BroodOptions(std::string name = "BroodOptions")
  :OESystem::OEOptions(name)
  {
    OESystem::OEStringParameter pDBName("-db");
    pDBName.SetRequired(true);
    pDBName.SetVisibility(OESystem::OEParamVisibility::Simple);
    pDBName.SetBrief("Database Folder");
    m_dbParam = AddParameter(pDBName);
    
    m_GeneralOptions = static_cast<OEBioisostere::OEBroodGeneralOptions*>(AddOption(OEBioisostere::OEBroodGeneralOptions()));
    m_ScoreOptions = static_cast<OEBioisostere::OEBroodScoreOptions*>(AddOption(OEBioisostere::OEBroodScoreOptions()));
    m_HitlistOptions = static_cast<OEBioisostere::OEBroodHitlistOptions*>(AddOption(OEBioisostere::OEBroodHitlistOptions()));
  }
  
  BroodOptions(const BroodOptions&) = default;
  BroodOptions& operator=(const BroodOptions&) = default;
  ~BroodOptions() override =default;
  BroodOptions* CreateCopy() const override { return new BroodOptions(*this);}
  
  std::string GetDataBase() const { return m_dbParam->GetStringValue(); }
  OEBioisostere::OEBroodGeneralOptions* GetGenOpts() const { return m_GeneralOptions; }
  OEBioisostere::OEBroodScoreOptions* GetScoreOpts() const { return m_ScoreOptions; }
  OEBioisostere::OEBroodHitlistOptions* GetHitlistOpts() const { return m_HitlistOptions; }
  
private:
  OESystem::OEParameter* m_dbParam;
  OEBioisostere::OEBroodGeneralOptions* m_GeneralOptions;
  OEBioisostere::OEBroodScoreOptions* m_ScoreOptions;
  OEBioisostere::OEBroodHitlistOptions* m_HitlistOptions;
};

int main(int argc, char* argv[])
{
  BroodOptions broodOpts;
  OEChem::OESimpleAppOptions opts(broodOpts, "BroodHitlist", OEChem::OEFileStringType::Mol3D, OEChem::OEFileStringType::Mol3D);
  
  if (OESystem::OEConfigureOpts(opts, argc, argv, false) == OESystem::OEOptsConfigureStatus::Help)
    return 0;
  broodOpts.UpdateValues(opts);
  
  OEChem::oemolistream ifs;
  if (!ifs.open(opts.GetInFile()))
    OESystem::OEThrow.Fatal("Unable to open %s for reading", opts.GetInFile().c_str());
  
  OEChem::oemolostream ofs;
  if (!ofs.open(opts.GetOutFile()))
    OESystem::OEThrow.Fatal("Unable to open %s for writing", opts.GetOutFile().c_str());
  
  OEBioisostere::OEBroodQuery query;
  bool retCode = OEBioisostere::OEReadBroodQuery(ifs,query);
  if (retCode != OEBioisostere::OEBroodStatusCode::Success)
    OESystem::OEThrow.Fatal("Failed: %", OEBioisostere::OEGetBroodStatus(retCode).c_str());
  
  OEBioisostere::OEDBReader reader;
  unsigned retValue = reader.Init(broodOpts.GetDataBase(), query, *broodOpts.GetGenOpts());
  if (retValue != OEBioisostere::OEBroodStatusCode::Success)
    OESystem::OEThrow.Fatal("Unable to load Brood database");
  
  OEBioisostere::OEBroodOverlay overlay = OEBioisostere::OEBroodOverlay(*broodOpts.GetGenOpts(), *broodOpts.GetScoreOpts());
  overlay.SetupRef(query);
  
  OEBioisostere::OEHitlistBuilder hlist = OEBioisostere::OEHitlistBuilder(query, *broodOpts.GetGenOpts(), *broodOpts.GetHitlistOpts());
  
  unsigned packetCount = 0;
  OEBioisostere::OEBroodDBPacket packet;
  while(reader.GetNextPacket(packet))
  {
    packetCount++;
    printf("Processing packet %d with %d fragments \n", packetCount, packet.GetFragCount());
    std::vector<OEBioisostere::OEBroodScore> vecScores = overlay.Overlay(packet);
    hlist.AddScores(vecScores);
  }
  printf("Generating hitlist... \n");
  hlist.Build();
  printf("Total number of fragments overlayed: %d \n", hlist.GetAddCount());
  printf("Number of final hits: %d \n", hlist.GetHitCount());
  
  std::vector<OEBioisostere::OEBroodHit> vecHits = hlist.GetHits();
  unsigned index = 0;
  for(const auto& hit:vecHits)
  {
    OEChem::OEWriteConstMolecule(ofs, hit.GetMol());
    double comboScore = hit.GetComboScore();
    printf("Hit: %d %s Combo Score: %2f Belief Score: %.2f Complexity: %2f \n", index+1, hit.GetMol().GetTitle(), comboScore, hit.GetBeliefScore(), hit.GetComplexity());
    index++;
  }
}

Download code

brood_hitlist.cpp

Generating Brood Matches

The following code example shows how to perform bioisosteric fragment replacements on a Brood query and generate all possible matches. This could be a use case when generating all possible design ideas using BROOD and postprocessing them with other tools.

See also

• OEBroodGeneralOptions class

• OEBroodScoreOptions class

• OEBroodOverlay class

• OEBroodMolBuilder class

Listing 4: Generating Brood Matches

/*
 (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.
 */
#include <cstdio>
#include <string>
#include <openeye.h>

#include <oeplatform.h>
#include <oesystem.h>
#include <oechem.h>
#include <oebioisostere.h>


class BroodOptions : public OESystem::OEOptions
{
public:
  BroodOptions(std::string name = "BroodOptions")
  :OESystem::OEOptions(name)
  {
    OESystem::OEStringParameter pDBName("-db");
    pDBName.SetRequired(true);
    pDBName.SetVisibility(OESystem::OEParamVisibility::Simple);
    pDBName.SetBrief("Database Folder");
    m_dbParam = AddParameter(pDBName);
    
    m_GeneralOptions = static_cast<OEBioisostere::OEBroodGeneralOptions*>(AddOption(OEBioisostere::OEBroodGeneralOptions()));
    m_ScoreOptions = static_cast<OEBioisostere::OEBroodScoreOptions*>(AddOption(OEBioisostere::OEBroodScoreOptions()));
    m_BuildOptions = static_cast<OEBioisostere::OEBroodBuildOptions*>(AddOption(OEBioisostere::OEBroodBuildOptions()));
  }
  
  BroodOptions(const BroodOptions&) = default;
  BroodOptions& operator=(const BroodOptions&) = default;
  ~BroodOptions() override =default;
  BroodOptions* CreateCopy() const override { return new BroodOptions(*this);}
  
  std::string GetDataBase() const { return m_dbParam->GetStringValue(); }
  OEBioisostere::OEBroodGeneralOptions* GetGenOpts() const { return m_GeneralOptions; }
  OEBioisostere::OEBroodScoreOptions* GetScoreOpts() const { return m_ScoreOptions; }
  OEBioisostere::OEBroodBuildOptions* GetBuildOpts() const { return m_BuildOptions; }

private:
  OESystem::OEParameter* m_dbParam;
  OEBioisostere::OEBroodGeneralOptions* m_GeneralOptions;
  OEBioisostere::OEBroodScoreOptions* m_ScoreOptions;
  OEBioisostere::OEBroodBuildOptions* m_BuildOptions;
};


int main(int argc, char* argv[])
{
  BroodOptions broodOpts;
  OEChem::OESimpleAppOptions opts(broodOpts, "BroodMatching", OEChem::OEFileStringType::Mol3D, OEChem::OEFileStringType::Mol3D);
  
  if (OESystem::OEConfigureOpts(opts, argc, argv, false) == OESystem::OEOptsConfigureStatus::Help)
    return 0;
  broodOpts.UpdateValues(opts);
  
  OEChem::oemolistream ifs;
  if (!ifs.open(opts.GetInFile()))
    OESystem::OEThrow.Fatal("Unable to open %s for reading", opts.GetInFile().c_str());
  
  OEChem::oemolostream ofs;
  if (!ofs.open(opts.GetOutFile()))
    OESystem::OEThrow.Fatal("Unable to open %s for writing", opts.GetOutFile().c_str());
  
  OEBioisostere::OEBroodQuery query;
  bool retCode = OEBioisostere::OEReadBroodQuery(ifs,query);
  if (retCode != OEBioisostere::OEBroodStatusCode::Success)
    OESystem::OEThrow.Fatal("Failed: %s", OEBioisostere::OEGetBroodStatus(retCode).c_str());
  
  OEBioisostere::OEDBReader reader;
  unsigned retValue = reader.Init(broodOpts.GetDataBase(), query, *broodOpts.GetGenOpts());
  if (retValue != OEBioisostere::OEBroodStatusCode::Success)
    OESystem::OEThrow.Fatal("Unable to load Brood database");
  
  OEBioisostere::OEBroodOverlay overlay = OEBioisostere::OEBroodOverlay(*broodOpts.GetGenOpts(), *broodOpts.GetScoreOpts());
  overlay.SetupRef(query);
  
  OEBioisostere::OEBroodMolBuilder builder = OEBioisostere::OEBroodMolBuilder(query, *broodOpts.GetGenOpts(), *broodOpts.GetBuildOpts());
  
  unsigned packetCount = 0;
  unsigned totalCount = 0;
  unsigned successCount = 0;
  OEBioisostere::OEBroodDBPacket packet;
  while(reader.GetNextPacket(packet))
  {
    packetCount++;
    printf("Processing packet %d with %d fragments \n", packetCount, packet.GetFragCount());
    std::vector<OEBioisostere::OEBroodScore> vecScores = overlay.Overlay(packet);
    for (const auto& score:vecScores)
    {
      totalCount++;
      if (score.GetStatus() == OEBioisostere::OEBroodStatusCode::Success)
      {
        OEBioisostere::OEBroodHit hit;
        if(builder.Build(score,hit)==OEBioisostere::OEBroodStatusCode::Success)
        {
          OEChem::OEWriteConstMolecule(ofs, hit.GetMol());
          successCount++;
        }
      }
    }
  }
  ofs.close();
  printf("Total number of fragments overlayed: %d \n",totalCount);
  printf("Number of successful matches: %d \n",successCount);
}

Download code

brood_matching.cpp

Overlay between Fragments

The following code example shows how to overlay a fragment against a query fragment. This could be a use case when working with synthons and trying to find similar synthons based on 3D similarity.

See also

• OEBroodGeneralOptions class

• OEBroodScoreOptions class

• OEFragOverlay class

Listing 5: Overlay between Fragments

/*
 (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.
 */
#include <cstdio>
#include <string>
#include <openeye.h>

#include <oeplatform.h>
#include <oesystem.h>
#include <oechem.h>
#include <oebioisostere.h>


int main(int argc, char* argv[])
{
  OEBioisostere::OEBroodGeneralOptions genOpts;
  OEChem::OERefInputAppOptions opts(genOpts, "FragmentOverlay", OEChem::OEFileStringType::Mol3D, OEChem::OEFileStringType::Mol3D, OEChem::OEFileStringType::Mol3D, "-queryFrag");

  if (OESystem::OEConfigureOpts(opts, argc, argv, false) == OESystem::OEOptsConfigureStatus::Help)
    return 0;
  genOpts.UpdateValues(opts);

  OEChem::oemolistream ifs;
  if (!ifs.open(opts.GetInFile()))
    OESystem::OEThrow.Fatal("Unable to open %s for reading", opts.GetInFile().c_str());

  OEChem::oemolistream rfs;
  if (!rfs.open(opts.GetRefFile()))
    OESystem::OEThrow.Fatal("Unable to open %s for reading", opts.GetInFile().c_str());

  OEChem::oemolostream ofs;
  if (!ofs.open(opts.GetOutFile()))
    OESystem::OEThrow.Fatal("Unable to open %s for writing", opts.GetOutFile().c_str());

  OEChem::OEMol query;
  if (!OEChem::OEReadMolecule(rfs, query))
    OESystem::OEThrow.Fatal("Failed to read Query fragment");

  OEBioisostere::OEBroodFragPrep prep;
  OEBioisostere::OEFragOverlay overlay = OEBioisostere::OEFragOverlay(genOpts,OEBioisostere::OEBroodScoreOptions());
  overlay.SetupRef(query);
  
  OEChem::OEMol mol;
  while (OEChem::OEReadMolecule(ifs, mol))
  {
    printf("Overlaying %s \n",mol.GetTitle());
    prep.Prep(mol);
    OEBioisostere::OEBroodScore score;
    unsigned retCode = overlay.Overlay(mol, score);
    if (retCode == OEBioisostere::OEBroodStatusCode::Success)
    {
      OEChem::OEGraphMol outmol;
      score.GetFragMol(outmol);
      overlay.Transform(outmol);
      double comboScore = score.GetComboScore();
      printf("Fragment: %s Combo Score: %.5f \n",mol.GetTitle(),comboScore);
      OEChem::OEWriteConstMolecule(ofs,outmol);
    }
    else
    {
      OESystem::OEThrow.Warning("%s: %s",mol.GetTitle(), OEBioisostere::OEGetBroodStatus(retCode).c_str());
    }
  }
  return 0;
}

Download code

fragment_overlay.cpp

Replacing a Fragment in a Molecule

The following code example shows how to replace a fragment in a molecule defined in the form of a BROOD query.

See also

• OEBroodGeneralOptions class

• OEBroodScoreOptions class

• OEBroodOverlay class

• OEBroodMolBuilder class

Listing 6: Replacing a Fragment in a Molecule

/*
 (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.
 */
#include <cstdio>
#include <string>
#include <openeye.h>

#include <oeplatform.h>
#include <oesystem.h>
#include <oechem.h>
#include <oebioisostere.h>

class BroodOptions : public OESystem::OEOptions
{
public:
  BroodOptions(std::string name = "BroodOptions")
  :OESystem::OEOptions(name)
  {
    m_GeneralOptions = static_cast<OEBioisostere::OEBroodGeneralOptions*>(AddOption(OEBioisostere::OEBroodGeneralOptions()));
    m_ScoreOptions = static_cast<OEBioisostere::OEBroodScoreOptions*>(AddOption(OEBioisostere::OEBroodScoreOptions()));
    m_BuildOptions = static_cast<OEBioisostere::OEBroodBuildOptions*>(AddOption(OEBioisostere::OEBroodBuildOptions()));
  }
  
  BroodOptions(const BroodOptions&) = default;
  BroodOptions& operator=(const BroodOptions&) = default;
  ~BroodOptions() override =default;
  BroodOptions* CreateCopy() const override { return new BroodOptions(*this);}
  OEBioisostere::OEBroodGeneralOptions* GetGenOpts() const { return m_GeneralOptions; }
  OEBioisostere::OEBroodScoreOptions* GetScoreOpts() const { return m_ScoreOptions; }
  OEBioisostere::OEBroodBuildOptions* GetBuildOpts() const { return m_BuildOptions; }
  
private:
  OEBioisostere::OEBroodGeneralOptions* m_GeneralOptions;
  OEBioisostere::OEBroodScoreOptions* m_ScoreOptions;
  OEBioisostere::OEBroodBuildOptions* m_BuildOptions;
};


int main(int argc, char* argv[])
{
  BroodOptions broodOpts;
  OEChem::OERefInputAppOptions opts(broodOpts, "ReplaceFragment", OEChem::OEFileStringType::Mol3D,OEChem::OEFileStringType::Mol3D, OEChem::OEFileStringType::Mol3D, "-query");
  
  if (OESystem::OEConfigureOpts(opts, argc, argv, false) == OESystem::OEOptsConfigureStatus::Help)
    return 0;
  broodOpts.UpdateValues(opts);
  
  OEChem::oemolistream ifs;
  if (!ifs.open(opts.GetInFile()))
    OESystem::OEThrow.Fatal("Unable to open %s for reading", opts.GetInFile().c_str());
  
  OEChem::oemolistream rfs;
  if (!rfs.open(opts.GetRefFile()))
    OESystem::OEThrow.Fatal("Unable to open %s for reading", opts.GetRefFile().c_str());
  
  OEChem::oemolostream ofs;
  if (!ofs.open(opts.GetOutFile()))
    OESystem::OEThrow.Fatal("Unable to open %s for writing", opts.GetOutFile().c_str());
  
  OEBioisostere::OEBroodQuery query;
  bool retCode = OEBioisostere::OEReadBroodQuery(rfs,query);
  if (retCode != OEBioisostere::OEBroodStatusCode::Success)
    OESystem::OEThrow.Fatal("Failed: %s", OEBioisostere::OEGetBroodStatus(retCode).c_str());
  
  OEBioisostere::OEBroodFragPrep prep;
  OEBioisostere::OEBroodOverlay overlay = OEBioisostere::OEBroodOverlay(*broodOpts.GetGenOpts(), *broodOpts.GetScoreOpts());
  overlay.SetupRef(query);
  
  OEBioisostere::OEBroodMolBuilder builder = OEBioisostere::OEBroodMolBuilder(query, *broodOpts.GetGenOpts(), *broodOpts.GetBuildOpts());
  
  OEChem::OEMol mol;
  while (OEChem::OEReadMolecule(ifs, mol))
  {
    printf("Replacement fragment %s \n",mol.GetTitle());
    prep.Prep(mol);
    OEBioisostere::OEBroodScore score;
    unsigned retCode = overlay.Overlay(mol, score);
    if (retCode == OEBioisostere::OEBroodStatusCode::Success)
    {
      double comboScore = score.GetComboScore();
      printf("Fragment: %s Combo Score: %.5f \n",mol.GetTitle(),comboScore);
      OEBioisostere::OEBroodHit hit;
      if(builder.Build(score, hit) == OEBioisostere::OEBroodStatusCode::Success)
        OEChem::OEWriteConstMolecule(ofs, hit.GetMol());
    }
    else
    {
      OESystem::OEThrow.Warning("%s: %s",mol.GetTitle(), OEBioisostere::OEGetBroodStatus(retCode).c_str());
    }
  }
  
  return 0;
}

Download code

replace_fragment.cpp

Building and Using an External Compound Database

The following code example shows how to build and use an external (in-house) compound database to find similar 2D compounds to a generated hit list. It demonstrates optional analog lookup against a user-provided compound database to annotate Brood hits with similar known molecules.

See also

• OECPDDatabase class

• OEBroodGeneralOptions class

• OEBroodScoreOptions class

• OEBroodOverlay class

• OEDBBuilder class

• OEDBWriter class

Listing 7: Building and using an external Compound Database

/*
 (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.
 */
#include <cstdio>
#include <openeye.h>

#include <oeplatform.h>
#include <oesystem.h>
#include <oechem.h>
#include <oebioisostere.h>


class BroodOptions : public OESystem::OEOptions
{
public:
  BroodOptions(std::string name = "BroodOptions")
  :OESystem::OEOptions(name)
  {
    OESystem::OEStringParameter pDBName("-db");
    pDBName.SetRequired(true);
    pDBName.SetVisibility(OESystem::OEParamVisibility::Simple);
    pDBName.SetBrief("Brood Database Directory");
    m_dbParam = AddParameter(pDBName);
    
    OESystem::OEStringParameter pCPDDBName("-cpddb");
    pCPDDBName.SetRequired(true);
    pCPDDBName.SetVisibility(OESystem::OEParamVisibility::Simple);
    pCPDDBName.SetBrief("CPDDatabase File (database of known compounds to identify available compounds similar to hits)");
    m_cpddbParam = AddParameter(pCPDDBName);
    
    m_GeneralOptions = static_cast<OEBioisostere::OEBroodGeneralOptions*>(AddOption(OEBioisostere::OEBroodGeneralOptions()));
    m_ScoreOptions = static_cast<OEBioisostere::OEBroodScoreOptions*>(AddOption(OEBioisostere::OEBroodScoreOptions()));
    m_HitlistOptions = static_cast<OEBioisostere::OEBroodHitlistOptions*>(AddOption(OEBioisostere::OEBroodHitlistOptions()));
  }
  
  BroodOptions(const BroodOptions&) = default;
  BroodOptions& operator=(const BroodOptions&) = default;
  ~BroodOptions() override =default;
  BroodOptions* CreateCopy() const override { return new BroodOptions(*this);}
  
  std::string GetDataBase() const { return m_dbParam->GetStringValue(); }
  std::string GetCPDDataBase() const { return m_cpddbParam->GetStringValue(); }
  OEBioisostere::OEBroodGeneralOptions* GetGenOpts() const { return m_GeneralOptions; }
  OEBioisostere::OEBroodScoreOptions* GetScoreOpts() const { return m_ScoreOptions; }
  OEBioisostere::OEBroodHitlistOptions* GetHitlistOpts() const { return m_HitlistOptions; }
  
private:
  OESystem::OEParameter* m_dbParam;
  OESystem::OEParameter* m_cpddbParam;
  OEBioisostere::OEBroodGeneralOptions* m_GeneralOptions;
  OEBioisostere::OEBroodScoreOptions* m_ScoreOptions;
  OEBioisostere::OEBroodHitlistOptions* m_HitlistOptions;
};

int main(int argc, char* argv[])
{
  BroodOptions broodOpts;
  OEChem::OESimpleAppOptions opts(broodOpts, "BroodCPDDB", OEChem::OEFileStringType::Mol3D, "oeb");
  
  if (OESystem::OEConfigureOpts(opts, argc, argv, false) == OESystem::OEOptsConfigureStatus::Help)
    return 0;
  broodOpts.UpdateValues(opts);
  
  OEChem::oemolistream ifs;
  if (!ifs.open(opts.GetInFile()))
    OESystem::OEThrow.Fatal("Unable to open %s for reading", opts.GetInFile().c_str());
  
  OEBioisostere::OEBroodQuery query;
  bool retCode = OEBioisostere::OEReadBroodQuery(ifs,query);
  if (retCode != OEBioisostere::OEBroodStatusCode::Success)
    OESystem::OEThrow.Fatal("Failed: %", OEBioisostere::OEGetBroodStatus(retCode).c_str());
  
  OEBioisostere::OEDBReader reader;
  unsigned retValue = reader.Init(broodOpts.GetDataBase(), query, *broodOpts.GetGenOpts());
  if (retValue != OEBioisostere::OEBroodStatusCode::Success)
    OESystem::OEThrow.Fatal("Unable to load Brood database");
  
  OEChem::oemolistream ifsCPDDB;
  if (!ifsCPDDB.open(broodOpts.GetCPDDataBase()))
    OESystem::OEThrow.Fatal("Unable to load Brood CPDDatabase file");
  
  OEBioisostere::OECPDDatabase cpddb;
  retValue = cpddb.Prep(ifsCPDDB);
  OESystem::OEThrow.Info("Prepration Mode: %s", OEBioisostere::OEGetBroodStatus(retValue).c_str());
  
  int numOfCPDDBMolecule = cpddb.GetNumMolecules();
  OESystem::OEThrow.Info("Number of molecules in CPDDatabse: %d", numOfCPDDBMolecule);
  
  if(retValue == OEBioisostere::OEBroodStatusCode::NewFPGenerated){
    OEChem::oemolostream ofsCPDDB;
    if (!ofsCPDDB.open(opts.GetOutFile()))
      OESystem::OEThrow.Fatal("Unable to open %s for writing the newly generated finegrprint" , opts.GetOutFile().c_str());
    
    if(cpddb.Write(ifsCPDDB, ofsCPDDB))
      OESystem::OEThrow.Info("Fingerprints are written in the %s. You can use this file in the future with -cpddb for improved efficiency over current useage.",ofsCPDDB.GetFileName().c_str());
    else
      OESystem::OEThrow.Warning("Fingerprint mismatch in writing updated -cpddb file.",ofsCPDDB.GetFileName().c_str());
  }
  
  OEBioisostere::OEBroodOverlay overlay = OEBioisostere::OEBroodOverlay(*broodOpts.GetGenOpts(), *broodOpts.GetScoreOpts());
  overlay.SetupRef(query);
  
  OEBioisostere::OEHitlistBuilder hlist = OEBioisostere::OEHitlistBuilder(query, *broodOpts.GetGenOpts(), *broodOpts.GetHitlistOpts());
  
  OEBioisostere::OEBroodDBPacket packet;
  while(reader.GetNextPacket(packet))
  {
    std::vector<OEBioisostere::OEBroodScore> vecScores = overlay.Overlay(packet);
    hlist.AddScores(vecScores);
  }
  printf("Generating hitlist... \n");
  hlist.Build();
  printf("Number of final hits: %d \n \n", hlist.GetHitCount());
  
  std::vector<OEBioisostere::OEBroodHit> vecHits = hlist.GetHits();
  
  for(const auto& hit:vecHits)
  {
    if (cpddb.IsPrepared()){
      std::vector<std::string> vecCpddbValues;
      cpddb.GetSimilarMolecules(hit.GetMol(), vecCpddbValues);
      if (!vecCpddbValues[0].empty())
        printf("Hit Mol (SMILES): %s \nAnalog Mol (SMILES): %s \nAnalog Mol Label: %s \n \n", OEChem::OEMolToSmiles(hit.GetMol()).c_str(),vecCpddbValues[0].c_str(),vecCpddbValues[1].c_str());
    }
  }
}

Download code

brood_cpddb.cpp

Creating Brood Query by Linking Two Molecules (Bridging)

The following code example shows how to create a Brood query from two molecules to find a suitable linker between the two using bioisosteric fragment replacements using Brood.

See also

• OEBroodQuery class

• OECreateBroodQuery function

Listing 8: Creating Brood Query by Linking Two Molecules (Bridging)

/*
 (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.
 */
#include <cstdio>
#include <string>
#include <openeye.h>

#include <oeplatform.h>
#include <oesystem.h>
#include <oechem.h>
#include <oebioisostere.h>


class QueryOptions : public OESystem::OEOptions
{
public:
  QueryOptions(std::string name = "2MolLinkerQueryOptions")
  :OESystem::OEOptions(name)
  {
    OESystem::OEUIntParameter idxNo1Param("-atomIndicesNo1");
    idxNo1Param.SetIsList(true);
    idxNo1Param.SetRequired(true);
    idxNo1Param.SetBrief("Index of atoms in fragment No.1");
    m_idxNo1Param = AddParameter(idxNo1Param);
    
    OESystem::OEUIntParameter idxNo2Param("-atomIndicesNo2");
    idxNo2Param.SetIsList(true);
    idxNo2Param.SetRequired(true);
    idxNo2Param.SetBrief("Index of atoms in fragment No.2");
    m_idxNo2Param = AddParameter(idxNo2Param);
    
    OEChem::OEFileStringParameter duParam("-du",OEChem::OEFileStringType::DU);
    duParam.SetBrief("Design unit containg protein target for bump check");
    m_duParam = AddParameter(duParam);
    
    OESystem::OEUIntParameter maskParam("-proteinMask", OEBio::OEDesignUnitComponents::TargetComplexNoSolvent);
    maskParam.SetBrief("Design unit mask to identify protein target");
    m_maskParam = AddParameter(maskParam);
    
    OEChem::OEFileStringParameter selectDUParam("-selectDU",OEChem::OEFileStringType::DU);
    selectDUParam.SetBrief("Design unit containg select protein for bump check");
    m_selectDUParam = AddParameter(selectDUParam);
    
    OESystem::OEUIntParameter maskSelectParam("-proteinSelectMask", OEBio::OEDesignUnitComponents::TargetComplexNoSolvent);
    maskSelectParam.SetBrief("Design unit mask to identify select protein target");
    m_maskSelectParam = AddParameter(maskSelectParam);
  }
  
  QueryOptions(const QueryOptions&) = default;
  QueryOptions& operator=(const QueryOptions&) = default;
  ~QueryOptions() override =default;
  QueryOptions* CreateCopy() const override { return new QueryOptions(*this);}
  
  std::vector<int> GetFirstMolIndices()
  {
    std::vector<int> indices;
    OESystem::OEIter<const std::string> Value = m_idxNo1Param->GetStringValues();
    for (;Value;++Value)
    {
      indices.push_back(std::stoi(Value));
    }
    return indices;
  }
  
  std::vector<int> GetSecondMolIndices()
  {
    std::vector<int> indices;
    OESystem::OEIter<const std::string> Value = m_idxNo2Param->GetStringValues();
    for (;Value;++Value)
    {
      indices.push_back(std::stoi(Value));
    }
    return indices;
  }
  
  bool GetDU(OEChem::OERefInputAppOptions opts, OEBio::OEDesignUnit& du)
  {
    OEPlatform::oeifstream ifs;
    if(!m_duParam->GetHasValue())
      return false;
    if(!ifs.open(m_duParam->GetStringValue()))
      OESystem::OEThrow.Fatal("Unable to open %s for reading", opts.GetInFile().c_str());

    if(!OEBio::OEReadDesignUnit(ifs, du))
      OESystem::OEThrow.Fatal("Unable to read design unit");
    return true;
  }
  
  int GetProteinMask()
  {
    if (m_maskParam->GetHasValue())
      return std::stoi(m_maskParam->GetStringValue());
    return std::stoi(m_maskParam->GetStringDefault());
  }

  bool GetSelectDU(OEChem::OERefInputAppOptions opts, OEBio::OEDesignUnit& selectDU)
  {
    OEPlatform::oeifstream ifs;
    if(!m_selectDUParam->GetHasValue())
      return false;
    if(!ifs.open(m_selectDUParam->GetStringValue()))
      OESystem::OEThrow.Fatal("Unable to open %s for reading", opts.GetInFile().c_str());
    
    if(!OEBio::OEReadDesignUnit(ifs, selectDU))
      OESystem::OEThrow.Fatal("Unable to read design unit");
    return true;
  }
  
  int GetSelectProteinMask()
  {
    if (m_maskSelectParam->GetHasValue())
      return std::stoi(m_maskSelectParam->GetStringValue());
    return std::stoi(m_maskSelectParam->GetStringDefault());
  }
private:
  OESystem::OEParameter* m_idxNo1Param;
  OESystem::OEParameter* m_idxNo2Param;
  OESystem::OEParameter* m_duParam;
  OESystem::OEParameter* m_maskParam;
  OESystem::OEParameter* m_selectDUParam;
  OESystem::OEParameter* m_maskSelectParam;
};

int main(int argc, char* argv[])
{
  QueryOptions queryOpts;
  OEChem::OERefInputAppOptions opts(queryOpts, "2MolLinkerBroodQuery", OEChem::OEFileStringType::Mol3D, OEChem::OEFileStringType::Mol3D,
                                    OEChem::OEFileStringType::Mol3D, "-in2");
  
  if (OESystem::OEConfigureOpts(opts, argc, argv, false) == OESystem::OEOptsConfigureStatus::Help)
    return 0;
  queryOpts.UpdateValues(opts);
  
  OEChem::oemolistream ifs;
  if (!ifs.open(opts.GetInFile()))
    OESystem::OEThrow.Fatal("Unable to open %s for reading", opts.GetInFile().c_str());
  
  OEChem::oemolistream rfs;
  if (!rfs.open(opts.GetRefFile()))
    OESystem::OEThrow.Fatal("Unable to open %s for reading", opts.GetRefFile().c_str());
  
  OEChem::oemolostream ofs;
  if (!ofs.open(opts.GetOutFile()))
    OESystem::OEThrow.Fatal("Unable to open %s for writing", opts.GetOutFile().c_str());
  
  OEChem::OEMol firstMol;
  if (!OEChem::OEReadMolecule(ifs,firstMol))
    OESystem::OEThrow.Fatal("Unable to load molecule 1");
  
  OEChem::OEMol secondMol;
  if (!OEChem::OEReadMolecule(rfs, secondMol))
    OESystem::OEThrow.Fatal("Unable to load molecule 2");
  
  std::vector<int> firstMolIndices = queryOpts.GetFirstMolIndices();
  std::vector<OEChem::OEAtomBase*> firstMolAtoms;
  for (const auto& idx:firstMolIndices)
  {
    OEChem::OEAtomBase* firstMolAtom;
    firstMolAtom = firstMol.GetAtom(OEChem::OEHasAtomIdx(idx));
    if (firstMolAtom == nullptr)
      OESystem::OEThrow.Fatal("Invalid atom index %d", idx);
    firstMolAtoms.push_back(std::move(firstMolAtom));
  }

  std::vector<int> secondMolIndices = queryOpts.GetSecondMolIndices();
  std::vector<OEChem::OEAtomBase*> secondMolAtoms;
  for (const auto& idx:secondMolIndices)
  {
    OEChem::OEAtomBase* secondMolAtom;
    secondMolAtom = secondMol.GetAtom(OEChem::OEHasAtomIdx(idx));
    if (secondMolAtom == nullptr)
      OESystem::OEThrow.Fatal("Invalid atom index %d", idx);
    secondMolAtoms.push_back(std::move(secondMolAtom));
  }
  
  OEChem::OEAtomBondSet firstMolSelection;
  firstMolSelection.AddAtoms(firstMolAtoms);
  
  OEChem::OEAtomBondSet secondMolSelection;
  secondMolSelection.AddAtoms(secondMolAtoms);
  
  
  OEBioisostere::OEBroodQuery query;
  OEBio::OEDesignUnit du;
  OEBio::OEDesignUnit selectDU;
  
  unsigned retCode;
  
  if (!queryOpts.GetDU(opts, du) && !queryOpts.GetSelectDU(opts, selectDU))
    retCode = OEBioisostere::OECreateBroodQuery(query, firstMol, secondMol, firstMolSelection, secondMolSelection);
  else if (!queryOpts.GetDU(opts, du) && queryOpts.GetSelectDU(opts, selectDU))
  {
    const bool passingProteinSelect = true;
    retCode = OEBioisostere::OECreateBroodQuery(query, firstMol, secondMol, firstMolSelection, secondMolSelection, selectDU, queryOpts.GetSelectProteinMask(), passingProteinSelect);
  }
  else if (!queryOpts.GetSelectDU(opts, selectDU))
    retCode = OEBioisostere::OECreateBroodQuery(query, firstMol, secondMol, firstMolSelection, secondMolSelection, du, queryOpts.GetProteinMask());
  else
    retCode = OEBioisostere::OECreateBroodQuery(query, firstMol, secondMol, firstMolSelection, secondMolSelection, du, queryOpts.GetProteinMask(), selectDU, queryOpts.GetSelectProteinMask());

  if(retCode != OEBioisostere::OEBroodStatusCode::Success)
    OESystem::OEThrow.Fatal("%s", OEBioisostere::OEGetBroodStatus(retCode).c_str());
  
  OEBioisostere::OEWriteBroodQuery(ofs, query);
}

Download code

brood_2molLinker_query.cpp

Clustering Brood Hits

The following code example shows how to cluster a generated Brood hit list using OEBroodClusterBuilder and OEBroodCluster. It demonstrates post-processing of hits into similarity clusters and cluster-level prioritization.

See also

• OEBroodGeneralOptions class

• OEBroodScoreOptions class

• OEBroodHitlistOptions class

• OEBroodOverlay class

• OEHitlistBuilder class

• OEBroodClusterBuilder class

• OEBroodCluster class

Listing 9: Clustering Brood Hits

/*
 (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.
 */
#include <cstdio>
#include <openeye.h>

#include <oeplatform.h>
#include <oesystem.h>
#include <oechem.h>
#include <oebioisostere.h>

class BroodOptions : public OESystem::OEOptions
{
public:
  BroodOptions(std::string name = "BroodOptions")
    : OESystem::OEOptions(name)
  {
    OESystem::OEStringParameter pDBName("-db");
    pDBName.SetRequired(true);
    pDBName.SetVisibility(OESystem::OEParamVisibility::Simple);
    pDBName.SetBrief("Database Folder");
    m_dbParam = AddParameter(pDBName);

    m_GeneralOptions = static_cast<OEBioisostere::OEBroodGeneralOptions*>(AddOption(OEBioisostere::OEBroodGeneralOptions()));
    m_ScoreOptions = static_cast<OEBioisostere::OEBroodScoreOptions*>(AddOption(OEBioisostere::OEBroodScoreOptions()));
    m_HitlistOptions = static_cast<OEBioisostere::OEBroodHitlistOptions*>(AddOption(OEBioisostere::OEBroodHitlistOptions()));
  }

  BroodOptions(const BroodOptions&) = default;
  BroodOptions& operator=(const BroodOptions&) = default;
  ~BroodOptions() override = default;
  BroodOptions* CreateCopy() const override { return new BroodOptions(*this); }

  std::string GetDataBase() const { return m_dbParam->GetStringValue(); }
  OEBioisostere::OEBroodGeneralOptions* GetGenOpts() const { return m_GeneralOptions; }
  OEBioisostere::OEBroodScoreOptions* GetScoreOpts() const { return m_ScoreOptions; }
  OEBioisostere::OEBroodHitlistOptions* GetHitlistOpts() const { return m_HitlistOptions; }

private:
  OESystem::OEParameter* m_dbParam;
  OEBioisostere::OEBroodGeneralOptions* m_GeneralOptions;
  OEBioisostere::OEBroodScoreOptions* m_ScoreOptions;
  OEBioisostere::OEBroodHitlistOptions* m_HitlistOptions;
};

int main(int argc, char* argv[])
{
  BroodOptions broodOpts;
  OEChem::OESimpleAppOptions opts(broodOpts, "BroodCluster", OEChem::OEFileStringType::Mol3D, OEChem::OEFileStringType::Mol3D);

  if (OESystem::OEConfigureOpts(opts, argc, argv, false) == OESystem::OEOptsConfigureStatus::Help)
    return 0;
  broodOpts.UpdateValues(opts);

  OEChem::oemolistream ifs;
  if (!ifs.open(opts.GetInFile()))
    OESystem::OEThrow.Fatal("Unable to open %s for reading", opts.GetInFile().c_str());

  OEChem::oemolostream ofs;
  if (!ofs.open(opts.GetOutFile()))
    OESystem::OEThrow.Fatal("Unable to open %s for writing", opts.GetOutFile().c_str());

  OEBioisostere::OEBroodQuery query;
  unsigned retCode = OEBioisostere::OEReadBroodQuery(ifs, query);
  if (retCode != OEBioisostere::OEBroodStatusCode::Success)
    OESystem::OEThrow.Fatal("Failed to read query: %s", OEBioisostere::OEGetBroodStatus(retCode).c_str());

  OEBioisostere::OEDBReader reader;
  unsigned retValue = reader.Init(broodOpts.GetDataBase(), query, *broodOpts.GetGenOpts());
  if (retValue != OEBioisostere::OEBroodStatusCode::Success)
    OESystem::OEThrow.Fatal("Unable to load Brood database");

  OEBioisostere::OEBroodOverlay overlay(*broodOpts.GetGenOpts(), *broodOpts.GetScoreOpts());
  overlay.SetupRef(query);

  OEBioisostere::OEHitlistBuilder hitlist(query, *broodOpts.GetGenOpts(), *broodOpts.GetHitlistOpts());

  unsigned packetCount = 0;
  OEBioisostere::OEBroodDBPacket packet;
  while (reader.GetNextPacket(packet))
  {
    ++packetCount;
    printf("Processing packet %u with %u fragments\n", packetCount, packet.GetFragCount());
    const std::vector<OEBioisostere::OEBroodScore>& vecScores = overlay.Overlay(packet);
    hitlist.AddScores(vecScores);
  }

  hitlist.Build();
  std::vector<OEBioisostere::OEBroodHit> vecHits = hitlist.GetHits();
  printf("Initial hit count: %u\n", static_cast<unsigned>(vecHits.size()));

  OEBioisostere::OEBroodClusterBuilder clBuilder(query);
  if (!clBuilder.Add(vecHits) || !clBuilder.Rank())
    OESystem::OEThrow.Fatal("Unable to build hit clusters");

  const std::vector<OEBioisostere::OEBroodCluster>& vecClusters = clBuilder.GetClusters();
  printf("Number of clusters: %u\n", static_cast<unsigned>(vecClusters.size()));

  unsigned written = 0;
  for (const auto& cluster : vecClusters)
  {
    const unsigned rank = cluster.GetRank();
    printf("Cluster %u: head=%s members=%u interest=%.3f\n",
           rank,
           cluster.GetHead().GetFragSmiles().c_str(),
           cluster.Count(),
           cluster.GetInterest());
  }

  for (const auto& cluster : vecClusters)
  {
    OEChem::OEWriteConstMolecule(ofs, cluster.GetHead().GetMol());
    ++written;
  }

  for (const auto& cluster : vecClusters)
  {
    for (const auto& hit : cluster.GetMembers())
    {
      OEChem::OEWriteConstMolecule(ofs, hit.GetMol());
      ++written;
    }
  }

  printf("Wrote %u clustered molecules to %s\n", written, opts.GetOutFile().c_str());
  return 0;
}

Download code

brood_cluster.cpp

Building Combined Hits from Different Queries of the Same Molecule with OEBroodComboBuilder

The following code example shows how to use two Brood queries for the same molecule, where the first query is used to select a limited set of primary hits (controlled by -primaryQueryMaxHits) and the second query uses OEBroodComboBuilder to generate all possible secondary (combo) hits from those selected primary hits. The second stage is bounded by -secondaryQueryMaxHits.

This example demonstrates a two-query combo workflow using -in and -in2: it builds primary hits from the first query, expands secondary combo hits from the second query, then clusters and ranks the resulting combo hits before writing the final output molecules.

See also

• OEDBReader class

• OEBroodOverlay class

• OEBroodMolBuilder class

• OEBroodComboBuilder class

• OEBroodClusterBuilder class

• OEBroodCluster class

Listing 10: Building Combined Hits from Different Queries of the Same Molecule with OEBroodComboBuilder

/*
 (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.
 */

#include <cstdio>
#include <vector>

#include <openeye.h>

#include <oechem.h>
#include <oebioisostere.h>
#include <oeplatform.h>
#include <oesystem.h>

class BroodComboOptions : public OESystem::OEOptions
{
public:
  BroodComboOptions(std::string name = "BroodComboOptions")
    : OESystem::OEOptions(name)
  {
    OESystem::OEStringParameter dbParam("-db");
    dbParam.SetRequired(true);
    dbParam.SetVisibility(OESystem::OEParamVisibility::Simple);
    dbParam.SetBrief("Database folder");
    m_dbParam = AddParameter(dbParam);

    OESystem::OEUIntParameter maxHitsParam("-primaryQueryMaxHits", 15);
    maxHitsParam.SetVisibility(OESystem::OEParamVisibility::Simple);
    maxHitsParam.SetBrief("Maximum number of primary hits collected from the first query");
    m_maxHitsParam = AddParameter(maxHitsParam);

    OESystem::OEUIntParameter secondaryMaxHitsParam("-secondaryQueryMaxHits", 15);
    secondaryMaxHitsParam.SetVisibility(OESystem::OEParamVisibility::Simple);
    secondaryMaxHitsParam.SetBrief("Maximum number of secondary combo hits collected for each primary hit");
    m_secondaryMaxHitsParam = AddParameter(secondaryMaxHitsParam);

  }

  BroodComboOptions(const BroodComboOptions&) = default;
  BroodComboOptions& operator=(const BroodComboOptions&) = default;
  ~BroodComboOptions() override = default;
  BroodComboOptions* CreateCopy() const override { return new BroodComboOptions(*this); }

  std::string GetDataBase() const { return m_dbParam->GetStringValue();}
  unsigned int GetPrimaryQueryMaxHits() const
  {
    if (m_maxHitsParam->GetHasValue())
      return static_cast<unsigned int>(std::stoi(m_maxHitsParam->GetStringValue()));
    return static_cast<unsigned int>(std::stoi(m_maxHitsParam->GetStringDefault()));
  }
  unsigned int GetSecondaryQueryMaxHits() const
  {
    if (m_secondaryMaxHitsParam->GetHasValue())
      return static_cast<unsigned int>(std::stoi(m_secondaryMaxHitsParam->GetStringValue()));
    return static_cast<unsigned int>(std::stoi(m_secondaryMaxHitsParam->GetStringDefault()));
  }
private:
  OESystem::OEParameter* m_dbParam;
  OESystem::OEParameter* m_maxHitsParam;
  OESystem::OEParameter* m_secondaryMaxHitsParam;
};

int main(int argc, char* argv[])
{
  BroodComboOptions broodOpts;
  OEChem::OERefInputAppOptions opts(
      broodOpts,
      "BroodComboBuilder",
      OEChem::OEFileStringType::Mol3D,
      OEChem::OEFileStringType::Mol3D,
      OEChem::OEFileStringType::Mol3D,
      "-in2");

  if (OESystem::OEConfigureOpts(opts, argc, argv, false) == OESystem::OEOptsConfigureStatus::Help)
    return 0;
  broodOpts.UpdateValues(opts);

  OEChem::oemolistream ifs1;
  if (!ifs1.open(opts.GetInFile()))
    OESystem::OEThrow.Fatal("Unable to open %s for reading", opts.GetInFile().c_str());

  OEChem::oemolistream ifs2;
  if (!ifs2.open(opts.GetRefFile()))
    OESystem::OEThrow.Fatal("Unable to open %s for reading", opts.GetRefFile().c_str());

  OEChem::oemolostream ofs;
  if (!ofs.open(opts.GetOutFile()))
    OESystem::OEThrow.Fatal("Unable to open %s for writing", opts.GetOutFile().c_str());

  OEBioisostere::OEBroodQuery query1;
  unsigned retCode = OEBioisostere::OEReadBroodQuery(ifs1, query1);
  if (retCode != OEBioisostere::OEBroodStatusCode::Success)
    OESystem::OEThrow.Fatal("Failed to read -in1 query: %s", OEBioisostere::OEGetBroodStatus(retCode).c_str());

  OEBioisostere::OEBroodQuery query2;
  retCode = OEBioisostere::OEReadBroodQuery(ifs2, query2);
  if (retCode != OEBioisostere::OEBroodStatusCode::Success)
    OESystem::OEThrow.Fatal("Failed to read -in2 query: %s", OEBioisostere::OEGetBroodStatus(retCode).c_str());

  // Build primary hits from the first query.
  std::vector<OEBioisostere::OEBroodHit> vecPrimaryHits;
  OEBioisostere::OEDBReader primaryReader;
  if (primaryReader.Init(broodOpts.GetDataBase()) != OEBioisostere::OEBroodStatusCode::Success)
    OESystem::OEThrow.Fatal("Unable to open database for primary query hits");
  OEBioisostere::OEBroodOverlay primaryOverlay;
  primaryOverlay.SetupRef(query1);
  OEBioisostere::OEBroodMolBuilder primaryBuilder(query1);
  OEBioisostere::OEBroodDBPacket primaryPacket;
  while (primaryReader.GetNextPacket(primaryPacket) && vecPrimaryHits.size() < broodOpts.GetPrimaryQueryMaxHits())
  {
    const std::vector<OEBioisostere::OEBroodScore>& vecMatches = primaryOverlay.Overlay(primaryPacket);
    for (const auto& match : vecMatches)
    {
      OEBioisostere::OEBroodHit hit;
      if (primaryBuilder.Build(match, hit) == OEBioisostere::OEBroodStatusCode::Success)
      {
        vecPrimaryHits.push_back(hit);
        if (vecPrimaryHits.size() >= broodOpts.GetPrimaryQueryMaxHits())
          break;
      }
    }
  }
  if (vecPrimaryHits.empty())
    OESystem::OEThrow.Fatal("Unable to build primary hits from -in1");

  unsigned totalSecondaryHits = 0;
  unsigned written = 0;
  std::vector<OEBioisostere::OEBroodHit> allSecondaryHits;

  // The attempt budget below bounds Build() calls per primary hit
  // regardless of success rate.
  unsigned int maxBuildAttempts = broodOpts.GetSecondaryQueryMaxHits() * 20;

  // For each primary hit from query1, run query2 as the reference query in combo mode.
  // The per-primary cap keeps each combo expansion bounded by -secondaryQueryMaxHits.
  for (const auto& primaryHit : vecPrimaryHits)
  {
    OEBioisostere::OEDBReader secondaryReader;
    if (secondaryReader.Init(broodOpts.GetDataBase()) != OEBioisostere::OEBroodStatusCode::Success)
      OESystem::OEThrow.Fatal("Unable to build secondary combo hits from -in2");
    // Build an overlay pipeline for query2, then combine each score with the current
    // primary hit via OEBroodComboBuilder.
    OEBioisostere::OEBroodOverlay secondaryOverlay;
    secondaryOverlay.SetupRef(query2);
    OEBioisostere::OEBroodComboBuilder secondaryBuilder(query2, primaryHit);

    std::vector<OEBioisostere::OEBroodHit> vecSecondaryHits;
    OEBioisostere::OEBroodDBPacket secondaryPacket;
    unsigned int buildAttempts = 0;
    bool done = false;
    // Stream the database packets; stop once this primary hit reaches its cap
    // or exhausts the attempt budget.
    while (secondaryReader.GetNextPacket(secondaryPacket) && !done)
    {
      const std::vector<OEBioisostere::OEBroodScore>& vecMatches = secondaryOverlay.Overlay(secondaryPacket);
      for (const auto& match : vecMatches)
      {
        OEBioisostere::OEBroodHit hit;
        // Combo build succeeds only when the secondary replacement can be merged with
        // the primary context for the current query2 reference.
        if (secondaryBuilder.Build(match, hit) == OEBioisostere::OEBroodStatusCode::Success)
        {
          vecSecondaryHits.push_back(hit);
          if (vecSecondaryHits.size() >= broodOpts.GetSecondaryQueryMaxHits())
          {
            done = true;
            break;
          }
        }
        ++buildAttempts;
        if (buildAttempts >= maxBuildAttempts)
        {
          done = true;
          break;
        }
      }
    }
    allSecondaryHits.insert(allSecondaryHits.end(), vecSecondaryHits.begin(), vecSecondaryHits.end());
  }

  if (!allSecondaryHits.empty())
  {
    // Cluster and rank all secondary hits before writing output molecules.
    OEBioisostere::OEBroodClusterBuilder clBuilder(query1);
    if (!clBuilder.Add(allSecondaryHits))
      OESystem::OEThrow.Fatal("Unable to cluster secondary combo hits");
    if (!clBuilder.Rank())
      OESystem::OEThrow.Fatal("Unable to rank secondary combo clusters");

    const std::vector<OEBioisostere::OEBroodCluster>& vecClusters = clBuilder.GetClusters();

    for (const auto& cluster : vecClusters)
    {
      OEChem::OEWriteConstMolecule(ofs, cluster.GetHead().GetMol());
      ++written;
      ++totalSecondaryHits;
    }

    for (const auto& cluster : vecClusters)
    {
      for (const auto& hit : cluster.GetMembers())
      {
        OEChem::OEWriteConstMolecule(ofs, hit.GetMol());
        ++written;
        ++totalSecondaryHits;
      }
    }
  }

  printf("Primary hits: %u\n", static_cast<unsigned>(vecPrimaryHits.size()));
  printf("Secondary combo hits: %u\n", totalSecondaryHits);
  printf("Wrote %u molecules to %s\n", written, opts.GetOutFile().c_str());
  return 0;
}

Download code

brood_combo_builder.cpp

Curating Scored Fragment Hits with OEScoreHitlist

The following code example shows how to collect scored fragment matches for a query and curate them with OEScoreHitlist.

This example demonstrates score-level deduplication and ranking prior to full molecule building.

See also

• OEDBReader class

• OEBroodOverlay class

• OEScoreHitlist class

• OEBroodScore class

Listing 11: Curating Scored Fragment Hits with OEScoreHitlist

/*
 (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.
 */

#include <cstdio>

#include <openeye.h>
#include <oeplatform.h>
#include <oesystem.h>
#include <oechem.h>
#include <oebioisostere.h>

// Demonstrates how to collect, curate, and write scored Brood fragment hits
// with OEScoreHitlist starting from a query and fragment database.

class BroodScoreHitlistOptions : public OESystem::OEOptions
{
public:
  BroodScoreHitlistOptions(std::string name = "BroodScoreHitlistOptions")
    : OESystem::OEOptions(name)
  {
    OESystem::OEStringParameter dbParam("-db");
    dbParam.SetRequired(true);
    dbParam.SetVisibility(OESystem::OEParamVisibility::Simple);
    dbParam.SetBrief("Brood database folder");
    m_dbParam = AddParameter(dbParam);

    OESystem::OEUIntParameter maxHitsParam("-maxScoreHits", 100);
    maxHitsParam.SetVisibility(OESystem::OEParamVisibility::Simple);
    maxHitsParam.SetBrief("Maximum number of unique scored fragments curated by OEScoreHitlist");
    m_maxHitsParam = AddParameter(maxHitsParam);

  }

  BroodScoreHitlistOptions(const BroodScoreHitlistOptions&) = default;
  BroodScoreHitlistOptions& operator=(const BroodScoreHitlistOptions&) = default;
  ~BroodScoreHitlistOptions() override = default;
  BroodScoreHitlistOptions* CreateCopy() const override { return new BroodScoreHitlistOptions(*this); }

  std::string GetDataBase() const { return m_dbParam->GetStringValue(); }

  unsigned int GetMaxScoreHits() const
  {
    if (m_maxHitsParam->GetHasValue())
      return static_cast<unsigned int>(std::stoi(m_maxHitsParam->GetStringValue()));
    return static_cast<unsigned int>(std::stoi(m_maxHitsParam->GetStringDefault()));
  }

private:
  OESystem::OEParameter* m_dbParam;
  OESystem::OEParameter* m_maxHitsParam;
};

int main(int argc, char* argv[])
{
  BroodScoreHitlistOptions broodOpts;
  OEChem::OESimpleAppOptions opts(
      broodOpts,
      "BroodScoreHitlist",
      OEChem::OEFileStringType::Mol3D,
      OEChem::OEFileStringType::Mol3D);

  if (OESystem::OEConfigureOpts(opts, argc, argv, false) == OESystem::OEOptsConfigureStatus::Help)
    return 0;
  broodOpts.UpdateValues(opts);

  OEChem::oemolistream ifs;
  if (!ifs.open(opts.GetInFile()))
    OESystem::OEThrow.Fatal("Unable to open %s for reading", opts.GetInFile().c_str());

  OEChem::oemolostream ofs;
  if (!ofs.open(opts.GetOutFile()))
    OESystem::OEThrow.Fatal("Unable to open %s for writing", opts.GetOutFile().c_str());

  OEBioisostere::OEBroodQuery query;
  unsigned retCode = OEBioisostere::OEReadBroodQuery(ifs, query);
  if (retCode != OEBioisostere::OEBroodStatusCode::Success)
    OESystem::OEThrow.Fatal("Failed to read query: %s", OEBioisostere::OEGetBroodStatus(retCode).c_str());

  // Read database packets and overlay them against the query.
  OEBioisostere::OEDBReader reader;
  if (reader.Init(broodOpts.GetDataBase(), query) != OEBioisostere::OEBroodStatusCode::Success)
    OESystem::OEThrow.Fatal("Unable to open Brood database '%s'", broodOpts.GetDataBase().c_str());

  OEBioisostere::OEBroodOverlay overlay;
  overlay.SetupRef(query);

  // Use OEScoreHitlist to deduplicate and rank scored fragment matches.
  OEBioisostere::OEScoreHitlist scoreHitlist(broodOpts.GetMaxScoreHits());

  unsigned packetCount = 0;
  OEBioisostere::OEBroodDBPacket packet;
  while (reader.GetNextPacket(packet))
  {
    ++packetCount;
    scoreHitlist.AddScores(overlay.Overlay(packet));
  }

  scoreHitlist.Build();

  printf("Database packets processed:    %u\n", packetCount);
  printf("Total scores added:            %u\n", scoreHitlist.GetAddCount());
  printf("Unique fragment matches:       %u\n", scoreHitlist.GetMatchCount());
  printf("Duplicate scores filtered:     %u\n", scoreHitlist.GetDuplicateCount());
  printf("Curated score hits:            %u\n", scoreHitlist.GetHitCount());

  // Write the curated fragment hits selected by the score hitlist.
  for (const auto& score : scoreHitlist.GetHits())
    OEChem::OEWriteConstMolecule(ofs, score.GetFrag());

  printf("Wrote %u molecules to %s\n", scoreHitlist.GetHitCount(), opts.GetOutFile().c_str());
  return 0;
}

Download code

brood_score_hitlist.cpp

Comparing Connection and Molecule Building Outcomes

The following code example shows how to compare connection-table construction and full molecule-building outcomes from curated scored fragments.

This example demonstrates use of OEMolCTBuilder, OEBroodMolBuilder, and OEBroodBuildResult for build diagnostics.

See also

• OEScoreHitlist class

• OEMolCTBuilder class

• OEBroodMolBuilder class

• OEBroodBuildResult class

Listing 12: Comparing Connection and Molecule Building Outcomes

/*
 (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.
 */

#include <cstdio>

#include <openeye.h>
#include <oeplatform.h>
#include <oesystem.h>
#include <oechem.h>
#include <oebioisostere.h>

// Demonstrates how to take curated Brood scores and inspect connection-table
// and molecule-building outcomes with OEMolCTBuilder, OEBroodMolBuilder, and
// OEBroodBuildResult.

class BroodConnectionMolBuilderOptions : public OESystem::OEOptions
{
public:
  BroodConnectionMolBuilderOptions(std::string name = "BroodConnectionMolBuilderOptions")
    : OESystem::OEOptions(name)
  {
    OESystem::OEStringParameter dbParam("-db");
    dbParam.SetRequired(true);
    dbParam.SetVisibility(OESystem::OEParamVisibility::Simple);
    dbParam.SetBrief("Brood database folder");
    m_dbParam = AddParameter(dbParam);

    OESystem::OEUIntParameter maxHitsParam("-maxScoreHits", 100);
    maxHitsParam.SetVisibility(OESystem::OEParamVisibility::Simple);
    maxHitsParam.SetBrief("Maximum number of curated scores used for CT and molecule building");
    m_maxHitsParam = AddParameter(maxHitsParam);

  }

  BroodConnectionMolBuilderOptions(const BroodConnectionMolBuilderOptions&) = default;
  BroodConnectionMolBuilderOptions& operator=(const BroodConnectionMolBuilderOptions&) = default;
  ~BroodConnectionMolBuilderOptions() override = default;
  BroodConnectionMolBuilderOptions* CreateCopy() const override { return new BroodConnectionMolBuilderOptions(*this); }

  std::string GetDataBase() const { return m_dbParam->GetStringValue(); }

  unsigned int GetMaxScoreHits() const
  {
    if (m_maxHitsParam->GetHasValue())
      return static_cast<unsigned int>(std::stoi(m_maxHitsParam->GetStringValue()));
    return static_cast<unsigned int>(std::stoi(m_maxHitsParam->GetStringDefault()));
  }

private:
  OESystem::OEParameter* m_dbParam;
  OESystem::OEParameter* m_maxHitsParam;
};

int main(int argc, char* argv[])
{
  BroodConnectionMolBuilderOptions broodOpts;
  OEChem::OESimpleAppOptions opts(
      broodOpts,
      "BroodConnectionMolBuilder",
      OEChem::OEFileStringType::Mol3D,
      OEChem::OEFileStringType::Mol3D);

  if (OESystem::OEConfigureOpts(opts, argc, argv, false) == OESystem::OEOptsConfigureStatus::Help)
    return 0;
  broodOpts.UpdateValues(opts);

  OEChem::oemolistream ifs;
  if (!ifs.open(opts.GetInFile()))
    OESystem::OEThrow.Fatal("Unable to open %s for reading", opts.GetInFile().c_str());

  OEChem::oemolostream ofs;
  if (!ofs.open(opts.GetOutFile()))
    OESystem::OEThrow.Fatal("Unable to open %s for writing", opts.GetOutFile().c_str());

  OEBioisostere::OEBroodQuery query;
  unsigned retCode = OEBioisostere::OEReadBroodQuery(ifs, query);
  if (retCode != OEBioisostere::OEBroodStatusCode::Success)
    OESystem::OEThrow.Fatal("Failed to read query: %s", OEBioisostere::OEGetBroodStatus(retCode).c_str());

  // Gather scored fragment matches for the query from the Brood database.
  OEBioisostere::OEDBReader reader;
  if (reader.Init(broodOpts.GetDataBase(), query) != OEBioisostere::OEBroodStatusCode::Success)
    OESystem::OEThrow.Fatal("Unable to open Brood database '%s'", broodOpts.GetDataBase().c_str());

  OEBioisostere::OEBroodOverlay overlay;
  overlay.SetupRef(query);

  // Curate the raw scores before running CT and molecule building.
  OEBioisostere::OEScoreHitlist scoreHitlist(broodOpts.GetMaxScoreHits());
  OEBioisostere::OEBroodDBPacket packet;
  while (reader.GetNextPacket(packet))
    scoreHitlist.AddScores(overlay.Overlay(packet));
  scoreHitlist.Build();

  if (scoreHitlist.GetHitCount() == 0)
  {
    OESystem::OEThrow.Warning("No fragments survived overlay scoring; nothing to build.");
    return 0;
  }

  // Compare connection building and molecule building on the curated scores.
  OEBioisostere::OEMolCTBuilder ctBuilder(query);
  OEBioisostere::OEBroodMolBuilder molBuilder(query);

  unsigned written = 0;
  unsigned failedBuild = 0;
  unsigned failedCT = 0;
  unsigned ctAttempts = 0;
  unsigned idx = 0;

  for (const auto& score : scoreHitlist.GetHits())
  {
    ++idx;

    // Rebuild the candidate connection table from the scored fragment.
    OEChem::OEGraphMol ctMol(score.GetFrag());
    const bool ctOk = ctBuilder.Build(ctMol);
    ++ctAttempts;
    if (!ctOk)
      ++failedCT;

    // Build the full Brood hit directly from the same scored fragment.
    OEBioisostere::OEBroodHit hit;
    const unsigned status = molBuilder.Build(score, hit);
    if (status != OEBioisostere::OEBroodStatusCode::Success)
    {
      ++failedBuild;
      printf("[%4u] Build(score) failed: status=%s, ct=%s\n",
             idx,
             OEBioisostere::OEGetBroodStatus(status).c_str(),
             ctOk ? "pass" : "fail");
      continue;
    }

    // Collect build diagnostics for reporting with OEBroodBuildResult.
    OEChem::OEGraphMol diagMol(score.GetFrag());
    OEBioisostere::OEBroodBuildResult result;
    const unsigned diagStatus = molBuilder.Build(diagMol, result);

    OEChem::OEWriteConstMolecule(ofs, hit.GetMol());
    ++written;

    printf("[%4u] ct=%s diagStatus=%-14s buildStatus=%-14s molTC=%.3f strain=%6.2f dStrain=%6.2f\n",
           idx,
           ctOk ? "pass" : "fail",
           OEBioisostere::OEGetBroodStatus(diagStatus).c_str(),
           OEBioisostere::OEGetBroodStatus(result.GetBuildStatus()).c_str(),
           result.GetMolTanimotoCombo(),
           result.GetLocalStrain(),
           result.GetDeltaLocalStrain());
  }

  printf("---- Summary ----\n");
  printf("Curated scores:          %u\n", scoreHitlist.GetHitCount());
  printf("Hits written:            %u\n", written);
  printf("Mol build failures:      %u\n", failedBuild);
  printf("CT checks attempted:     %u\n", ctAttempts);
  printf("CT build failures:       %u\n", failedCT);
  return 0;
}

Download code

brood_connection_mol_builder.cpp