Molecule Fragmentation

The OEMedChem TK currently provides four ways to partition a molecule into fragments:

• OEGetRingChainFragments - fragments a molecule into ring and chain components.

• OEGetRingLinkerSideChainFragments - fragments a molecule into ring, linker and side-chain components as defined in [Bemis-1996] .

• OEGetFuncGroupFragments - fragments a molecule into ring and functional group components.

• OEGetBemisMurcko - fragments a molecule into ring, linker, framework and functional group components as in [Bemis-1996] .

These functions return an iterator over OEAtomBondSet objects that store the atoms and the bonds of the fragments.

The following examples (Listing 1, Listing 2) show how to fragment a molecule into ring and chain components. The code loops over the OEAtomBondSet objects returned by the OEGetRingChainFragments. Each OEAtomBondSet object is used to initialize an atom and a bond predicates. These predicates specify which atoms and bonds have to be considered when creating a subset of the molecule, i.e the fragment, when calling the OESubsetMol function. See the depiction of the input molecule and the generated fragments in Figure: Example of fragmentation.

Listing 1: Example of molecule fragmentation

using System;
using OpenEye.OEMedChem;
using OpenEye.OEChem;

public class FragRingChain
{
    public static int Main(string[] args)
    {
        OEGraphMol mol = new OEGraphMol();
        OEChem.OESmilesToMol(mol, "COc1ccc(cc1)CC(=O)N");

        foreach (OEAtomBondSet abset in OEMedChem.OEGetRingChainFragments(mol))
        {
            OEIsAtomMember fragatompred = new OEIsAtomMember(abset.GetAtoms());
            OEIsBondMember fragbondpred = new OEIsBondMember(abset.GetBonds());

            OEGraphMol fragment = new OEGraphMol();
            bool adjustHCount = true;
            OEChem.OESubsetMol(fragment, mol, fragatompred, fragbondpred, adjustHCount);
            Console.WriteLine(OEChem.OEMolToSmiles(fragment));
        }
        return 0;
    }
}

The output of Listing 1 is the following:

CO
c1ccccc1
CC(=O)N

Example of fragmentation (A) input molecule (B) fragments returned by the OEGetRingChainFragments function

See also

• OEAtomBondSet class and OESubsetMol function in the OEChem TK manual

• Predicate Functors chapter in the OEChem TK manual.

The following example (Listing 2) shows how to fragment a molecule into ring and chain components with annotations. See the depiction of the input molecule and the generated fragments in Figure: Example of Bemis Murcko fragmentation.

Listing 2: Example of molecule fragmentation with annotations

using System;
using OpenEye.OEMedChem;
using OpenEye.OEChem;

public class OEGetBemisMurcko
{
    public static int Main(string[] args)
    {
        OEGraphMol mol = new OEGraphMol();
        OEChem.OESmilesToMol(mol, "CCOc1ccc(cc1)CC(OC)c2ccccc2CC(=O)N");

        foreach (OEAtomBondSet abset in OEMedChem.OEGetBemisMurcko(mol))
        {
            OEIsAtomMember fragatompred = new OEIsAtomMember(abset.GetAtoms());
            OEIsBondMember fragbondpred = new OEIsBondMember(abset.GetBonds());

            OEGraphMol fragment = new OEGraphMol();
            bool adjustHCount = true;
            OEChem.OESubsetMol(fragment, mol, fragatompred, fragbondpred, adjustHCount);
            foreach (OERole role in abset.GetRoles())
            {
              Console.WriteLine("{0} {1}", role.GetName(), OEChem.OEMolToSmiles(fragment));
            }
        }
        return 0;
    }
}

The output of Listing 2 is the following:

Framework c1ccc(cc1)CCc2ccccc2
Ring c1ccccc1.c1ccccc1
Linker CC
Sidechain CCO.CC(=O)N.CO

Example of Bemis Murcko fragmentation

The following example (Listing 3) shows how to fragment a molecule and include unsaturated hetero bonds on the main framework. See the depiction of the input molecule and the generated fragments in Figure: Example of custom Bemis Murcko fragmentation including heteroatoms.

Listing 3: Example of custom molecule fragmentation

using System;
using OpenEye.OEMedChem;
using OpenEye.OEChem;

public class OEGetBemisMurckoUnsatHeteroBonds
{
    public static int Main(string[] args)
    {
        OEGraphMol mol = new OEGraphMol();
        OEChem.OESmilesToMol(mol, "CCc1nc(nc(n1)OC)NC(=O)NS(=O)(=O)c2ccccc2OC");
        OEBemisMurckoOptions options = new OEBemisMurckoOptions();
        options.SetUnsaturatedHeteroBonds(true);

        foreach (OEAtomBondSet abset in OEMedChem.OEGetBemisMurcko(mol, options))
        {
            OEIsAtomMember fragatompred = new OEIsAtomMember(abset.GetAtoms());
            OEIsBondMember fragbondpred = new OEIsBondMember(abset.GetBonds());

            OEGraphMol fragment = new OEGraphMol();
            bool adjustHCount = true;
            OEChem.OESubsetMol(fragment, mol, fragatompred, fragbondpred, adjustHCount);
            foreach (OERole role in abset.GetRoles())
            {
              Console.WriteLine("{0} {1}", role.GetName(), OEChem.OEMolToSmiles(fragment));
            }
        }
        return 0;
    }
}

The output of Listing 3 is the following:

Framework c1ccc(cc1)S(=O)(=O)NC(=O)Nc2ncncn2
Ring c1ccccc1.c1ncncn1
Linker C(=O)(N)NS(=O)=O
Sidechain CC.CO.CO

Example of Bemis Murcko fragmentation including unsaturated hetero bonds on main framework.

The following example (Listing 4) shows how to fragment a molecule and include custom sidechains on the main framework. See the depiction of the input molecule and the generated fragments in Figure: Example of custom Bemis Murcko fragmentation including custom substituents.

Listing 4: Example of custom molecule fragmentation

using System;
using OpenEye.OEMedChem;
using OpenEye.OEChem;

public class OEGetBemisMurckoCustomSubstituents
{
    public static int Main(string[] args)
    {
        OEGraphMol mol = new OEGraphMol();
        OEChem.OESmilesToMol(mol, "CCc1nc(nc(n1)OC)NC(CC(=O)N)NS(=O)(=O)c2ccccc2CC(=O)N"); 
        OESubSearch subsearch = new OESubSearch();
        subsearch.Init("[#6]-CC(=O)N");
        OEBemisMurckoOptions options = new OEBemisMurckoOptions();
        options.SetSubstituentSearch(subsearch);

        foreach (OEAtomBondSet abset in OEMedChem.OEGetBemisMurcko(mol, options))
        {
            OEIsAtomMember fragatompred = new OEIsAtomMember(abset.GetAtoms());
            OEIsBondMember fragbondpred = new OEIsBondMember(abset.GetBonds());

            OEGraphMol fragment = new OEGraphMol();
            bool adjustHCount = true;
            OEChem.OESubsetMol(fragment, mol, fragatompred, fragbondpred, adjustHCount);
            foreach (OERole role in abset.GetRoles())
            {
              Console.WriteLine("{0} {1}", role.GetName(), OEChem.OEMolToSmiles(fragment));
            }
        }
        return 0;
    }
}

The output of Listing 4 is the following:

Framework c1ccc(c(c1)CC(=O)N)[SH4]NC(CC(=O)N)Nc2ncncn2
Ring c1ccc(cc1)CC(=O)N.c1ncncn1
Linker C(C(N)N[SH5])C(=O)N
Sidechain CC.CO.O.O

Example of Bemis Murcko fragmentation including custom substituents on framework