Identifying Acceptor and Donor Atoms

Problem

You want to identify acceptor and donor atoms in a molecule.

**Table 1. Example of Lipinsky definitions (acceptor on the left, donor on the right)**

Ingredients

OEChem TK - cheminformatics toolkit

Difficulty Level

Solution

While the MolProp TK provides the functions to count the number of acceptor and donor atoms in the molecules, it does not identify which atoms are counted.

Lipinski [Lipinski-1997] provides a simple way to identify them. A Lipinski acceptor is either an oxygen or a nitrogen:

class IsLipinskiAcceptor(oechem.OEUnaryAtomPred):
    def __call__(self, atom):
        if atom.GetAtomicNum() in [oechem.OEElemNo_O, oechem.OEElemNo_N]:
            return True
        return False

A Lipinski donor is either an oxygen or a nitrogen with at least one hydrogen.

class IsLipinskiDonor(oechem.OEUnaryAtomPred):
    def __call__(self, atom):
        if atom.GetAtomicNum() not in [oechem.OEElemNo_O, oechem.OEElemNo_N]:
            return False
        return has_hydrogen(atom)

Where has_hydrogen is defined as the following to handle both implicit and explicit hydrogens:

def has_hydrogen(atom):

    if atom.GetImplicitHCount() > 0:
        return True
    for neigh in atom.GetAtoms():
        if neigh.IsHydrogen():
            return True
    return False

After implementing the definitions as predicates we can use them in any APIs that takes atom predicates. For example:

def num_lipinsky_acceptors(mol):
    return oechem.OECount(mol, IsLipinskiAcceptor())

def print_lipinsky_donors(mol):
    oechem.OETriposAtomTypeNames(mol)
    print("Lipinski donor atoms in molecule '{}'".format(oechem.OEMolTSmiles(mol)))
    for atom in mol.GetAtoms(IsLipinskiDonor()):
        print(atom.GetName())

For more information see Predicate Functors chapter of the OEChem TK manual.

Discussion

Another possible implementation is based on Daylight SMARTS definitions.

This following predicate only identifies hydrogen bond acceptor atoms in carbonyl and nitroso functional groups:

class IsHBondAcceptorCarbonylNitroso(oechem.OEUnaryAtomPred):
    # [#6,#7;R0]=[#8]
    def __call__(self, atom):
        if not atom.IsOxygen():
            return False
        if atom.GetHvyDegree() != 1:
            return False

        for bond in atom.GetBonds():
            if bond.GetOrder() != 2:
                return False
        for neigh in atom.GetAtom():
            if neigh.GetAtomicNum not in [oechem.OEElemNo_O, oechem.OEElemNo_N]:
                return False

        return True

The following predicate identifies hydrogen bond donor as either a nitrogen, oxygen or fluorine atom with at least one hydrogen:

class IsHBondDonor(oechem.OEUnaryAtomPred):
    # [!H0;#7,#8,#9]
    def __call__(self, atom):
        if atom.GetAtomicNum() not in [oechem.OEElemNo_O, oechem.OEElemNo_N, oechem.OEElemNo_F]:
            return False
        return has_hydrogen(atom)

The following predicate identifies hydrogen bond donor as a non-negatively charged hetero-atom with at least one hydrogen:

class IsHBondDonorInclusive(oechem.OEUnaryAtomPred):
    # [!$([#6,H0,-,-2,-3])]
    def __call__(self, atom):

        if atom.GetAtomicNum() in [oechem.OEElemNo_C, oechem.OEElemNo_H]:
            return False
        if atom.GetFormalCharge() != 0:
            return False

        return has_hydrogen(atom)

Also if a SMARTS pattern exists, it is very easy to create a predicate using the OEMatchAtom built-in predicate:

def print_donors(mol):
    oechem.OETriposAtomNames(mol)
    donorpred = oechem.OEMatchAtom("[!H0;#7,#8,#9]")
    print("Donor atoms in molecule '{}'".format(oechem.OEMolToSmiles(mol)))
    for atom in mol.GetAtoms(donorpred):
        print(atom.GetName())

For comparison, the simplified SMARTS definitions of acceptor and donor atoms in OpenEye’s ROCS application are the following:

donor: [$([#7,#8,#15,#16]);H]
acceptor: [#8&!$(\*~N~[OD1]),#7&H0;!$([D4]);!$([D3]-\*=,:[$([#7,#8,#15,#16])])]

Please note that the built-in Mills and Dean [MillsDean-1996] definitions used in ROCS are significantly more precise and elaborate.

Figure 1. Example of color definition in ROCS

Identifying Acceptor and Donor Atoms

Problem

Ingredients

Difficulty Level

Solution

Discussion

See also in OEChem TK manual

See also in OEMolProp TK manual

See also