Thursday, 18 January 2018

Implementing the Sayle tautomer hash with Open Babel

One of the consequences of last year's overhaul of handling of kekulization, aromaticity and implicit hydrogens is the ability to easily calculate structure hashes such as Roger Sayle's tautomer hash, which I wrote up on the NextMove blog a while ago.

I routinely use this hash to handle tautomers, particularly when dealing with R groups. It doesn't solve all tautomer issues (e.g. ones that involve carbon) but it can quickly bring you from having no support for handling tautomers to getting you 95% of the way. In fact, I've been thinking about adding this (and some of the other hashes that Roger has come up with) as cansmi output options. Anyhoo, here's an implementation in Python:
import pybel
ob = pybel.ob

def tautomerhash(smi):
    """Take a SMILES and return the Sayle tautomer hash:
    https://nextmovesoftware.com/blog/2016/06/22/fishing-for-matched-series-in-a-sea-of-structure-representations/
    """
    mol = pybel.readstring("smi", smi).OBMol
    mol.DeleteHydrogens() # just in case
    formalcharges = 0
    hcount = 0
    for atom in ob.OBMolAtomIter(mol):
        formalcharges += atom.GetFormalCharge()
        atom.SetFormalCharge(0)
        if atom.GetAtomicNum() != 6: # non-carbon
            hcount += atom.GetImplicitHCount()
        atom.SetImplicitHCount(0)
        atom.UnsetAromatic()
    for bond in ob.OBMolBondIter(mol):
        bond.SetBondOrder(1)
        bond.UnsetAromatic()
    mol.SetAromaticPerceived() # no point triggering perception
    return "%s_%d" % (pybel.Molecule(mol).write("can").rstrip(), hcount-formalcharges)

if __name__ == "__main__":
    smis = ["*c1c(c(C(=N)O)cc2nc([nH]c12)C(=O)[O-])N(=O)=O",
            "*c1c(c(C(=O)N)cc2[nH]c(nc12)C(=O)O)[N+](=O)[O-]"]
    for smi in smis:
        print(tautomerhash(smi))
The two SMILES in the example code above are those from the original blog post. Here they give the following two identical hashes (note to self: 'fix' the bracketed asterisk):
[O][C]([C]1[N][C]2[C]([N]1)[C]([*])[C]([C]([C]2)[C]([O])[N])N([O])[O])[O]_4
[O][C]([C]1[N][C]2[C]([N]1)[C]([*])[C]([C]([C]2)[C]([O])[N])N([O])[O])[O]_4

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