HI Stephen, Further to Greg's excellent reply, see this paper on how InChI strings and keys can be used in practice to map together tautomer (ones covered by InChI at least), isotope, stereo and parent-salt variants. http://rd.springer.com/article/10.1186/s13321-014-0043-5
Francis (cc'ed) has a nice notebook somewhere illustrating these nice InChI splits to find these variants. For educational purposes, there have been other approaches like the NCI's identifiers - discussion here: http://acscinf.org/docs/meetings/237nm/presentations/237nm17.pdf For pure structure standardization using RDKit see here: https://github.com/flatkinson/standardiser and https://github.com/mcs07/MolVS Cheers, George On 29 November 2016 at 17:02, Greg Landrum <greg.land...@gmail.com> wrote: > Wow, this is a great question and quite a fun thread. > > It's hard to really make much of a contribution here without writing a > book/review article (something that I'm really not willing to do!), but I > have a few thoughts. Most of this is repeating/rephrasing things others > have already said. > > I'm going to propose some things as facts. I think that these won't be > controversial: > fact 1: if the structures are coming from different sources, they need to > be standardized/normalized before you compare them. This is true regardless > of how you want to compare them. The details of the standardization process > are not incredibly important, but it does need to take care of the things > you care about when comparing molecules. For example, if you don't care > about differences between salts, it should strip salts. If you don't care > about differences between tautomers, it should normalize tautomers. > fact 2: The InChI algorithm includes a standardization step that > normalizes some tautomers, but does not remove salts. > fact 3: The InChI representation contain a number of layers defining the > structure in increasing detail (this isn't strictly true, because some of > the choices about how layers are ordered are arbitrary, but it's close). > fact 4: canonicalization, the way I define it, produces a canonical atom > numbering for a given structure, but it does *not* standardize > fact 5: the RDKit has essentially no well-documented standardization code > > fact X: we don't have any standard, broadly accepted approach for > standardization, canonicalization or representation that is fool-proof or > that works for even all of organic chemistry, never mind organometallics. > InChI, useful as it is for some things, completely fails to handle things > like atropisomers (they are working on this kind of thing, but it's not out > yet). > > Given all of this, if I wanted to have flexible duplicate checking *right* > now, I think I would use the AvalonTools struchk functionality that the > RDKit provides (the new pure-RDKit version still needs a bit more testing) > to handle basic standardization and salt stripping and then produce a table > that includes the InChI in a couple of different forms. I'd want to be able > to recognize molecules that differ only by stereochemistry, molecules that > differ only by location of tautomeric Hs, and molecules that differ only by > the location of isotopic labels. You can do this with various clever splits > of the InChI (how to do it is left as an exercise for the reader and/or a > future RDKit blog post). > > I think there's something fun to be done here with SMILES variants, > borrowing heavily from some of the things that Roger has written about: > https://nextmovesoftware.com/blog/2013/04/25/finding-all-typ > es-of-every-mer/ > here's a more recent application of that from Noel: > https://nextmovesoftware.com/blog/2016/06/22/fishing-for-mat > ched-series-in-a-sea-of-structure-representations/ > > If I didn't really care about details and just wanted something that I > could explain easily to others, I'd skip all the complication and just use > InChIs (or InChI keys) to recognize duplicates. There would be times when > that would be the wrong answer, but it would be a broadly accepted kind of > wrong.[1] > > Regardless of the approach, I would not, under most any circumstances, > discard the original input structures that I had. It's really good to be > able to figure out what the original data looked like later. > > -greg > [1] I'm crying as I write this... > > > > > On Mon, Nov 28, 2016 at 5:25 PM, Stephen O'hagan <soha...@manchester.ac.uk > > wrote: > >> Has anyone come up with fool-proof way of matching structurally >> equivalent molecules? >> >> >> >> Unique Smiles or InChI String comparisons don’t appear to work presumable >> because there are different but equivalent structures, e.g. explicit vs >> non-explicit H’s, Kekule vs Aromatic, isomeric forms vs non-isomeric form, >> tautomers etc. >> >> >> >> I also expect that comparing InChI strings might need something more than >> just a simple string comparison, such as masking off stereo information >> when you don’t care about stereo isomers. >> >> >> >> I assume there are suitable tools within RDKit that can do this? >> >> >> >> N.B. I need to collate tables from several sources that have a mix of >> smiles / InChI / sdf molecular representations. >> >> >> >> I usually use RDKit via Python and/or Knime. >> >> >> >> Cheers, >> >> Steve. >> >> >> >> ------------------------------------------------------------ >> ------------------ >> >> _______________________________________________ >> Rdkit-discuss mailing list >> Rdkit-discuss@lists.sourceforge.net >> https://lists.sourceforge.net/lists/listinfo/rdkit-discuss >> >> > > ------------------------------------------------------------ > ------------------ > > _______________________________________________ > Rdkit-discuss mailing list > Rdkit-discuss@lists.sourceforge.net > https://lists.sourceforge.net/lists/listinfo/rdkit-discuss > >
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