Bug in SMARTS queries

[eahenle]

Given an input SMILES string and SMARTS query from the MACCS fingerprinting scheme (we are trying to implement this fingerprinting for the package) we found the following issue:

using MolecularGraph
mol = smilestomol("CCOP(=S)(OCC)Oc1cc(C)nc(C(C)C)n1")
query = smartstomol("[#6]=[#6](~[!#6;!#1])~[!#6;!#1]")
hassubstructmatch(mol, query) # returns true, but should return false!

Looking at the substructure match in Pluto, we see this:

begin
    matched1 = Set(Iterators.flatten(keys(m) for m in substructmatches(mol, query)))
    subg1 = MolecularGraph.nodesubgraph(mol, matched1)
    svg1 = MolecularGraph.drawsvg(mol, 300, 300, highlight=subg1)
    HTML(svg1)
end

This shows, I think, two problems:

• The aromatic bonds are being assigned to single and double bonds and matched as such (even though they are also correctly identified as aromatic in other queries on the same structure)
• The branching is not being handled correctly (the SMARTS query specifies that carbon must be bonded to two non-carbon atoms, but there is only one; it must be double-counting the nitrogen or mis-identifying the methyl carbon)

This is one example, but for this single structure, there are many MACCS keys that return false positive.

[mojaie]

Thank you for the catch. Maybe SMARTS query is still not compatible with some advanced queries. I'm working on SMARTS in dev branch. Later I will check the current state.

[mojaie]

MACCS fingerprinting scheme (we are trying to implement this fingerprinting for the package)

I'm very happy to hear that!

[eahenle]

Here is the complete list of MACCS rules that are returning false-positive for the molecule shown above.

Each rule is a tuple that gives the SMARTS query and the count of matches that must be exceeded to turn the bit "on".

Tuple{String, Int64}[
("[#6]=[#6](~[!#6;!#1])~[!#6;!#1]", 0),
("[!#6;!#1]~[CH2]~[!#6;!#1]", 0),
("[!#6;!#1;!H0]~*~[!#6;!#1;!H0]", 0),
("[!#1;!#6;!#7;!#8;!#9;!#14;!#15;!#16;!#17;!#35;!#53]", 0),
("[#6]=[#6]~[#7]", 0),
("[!#6;!#1;!H0]~*~*~*~[!#6;!#1;!H0]", 0),
("[!#6;!#1;!H0]~*~*~[!#6;!#1;!H0]", 0),
("[!#6;!#1;!H0]~[!#6;!#1;!H0]", 0),
("[!#6;!#1]~[!#6;!#1;!H0]", 0),
("[!#6;!#1]~[#7]~[!#6;!#1]", 0),
("[#6]=[#6](~*)~*", 0),
("[#6]=[#7]", 0),
("*~[CH2]~[!#6;!#1;!H0]", 0),
("[C;H2,H3][!#6;!#1][C;H2,H3]", 0),
("[\$([!#6;!#1;!H0]~*~*~[CH2]~*),\$([!#6;!#1;!H0;R]1@[R]@[R]@[CH2;R]1),\$([!#6;!#1;!H0]~[R]1@[R]@[CH2;R]1)]", 0),
("[\$([!#6;!#1;!H0]~*~*~*~[CH2]~*),\$([!#6;!#1;!H0;R]1@[R]@[R]@[R]@[CH2;R]1),\$([!#6;!#1;!H0]~[R]1@[R]@[R]@[CH2;R]1),\$([!#6;!#1;!H0]~*~[R]1@[R]@[CH2;R]1)]", 0),
("[!#6;!#1]~[CH3]", 0),
("[!#6;!#1]~[#7]", 0),
("[#6]=[#6]", 0),
("[!#6;!#1;!H0]~*~[CH2]~*", 0),
("[#7]=*", 0),
("[!#6;!#1;!H0]", 1),
("*1~*~*~*~*~*~1", 1),
("[#6]-[#7]", 0)
]

[mojaie]

@eahenle queries you listed seems to return false at the new version (I checked it with v0.14.2).