3 ms·

if InChI doesn't do it for you, i suppose SMILES[1] isn't sufficient either? By-the-bye, you're not ever going to be able to "concisely" encode 3d (or even 2d

if InChI doesn't do it for you, i suppose SMILES[1] isn't sufficient either? By-the-bye, you're not ever going to be able to "concisely" encode 3d (or even 2d coordinate) structures, because there isn't just one such. They're a thermally sampled average of structures. [1] https://en.wikipedia.org/wiki/Simplified_molecular-input_line-entry_system https://en.wikipedia.org/wiki/Simplified_molecular-input_lin...

dalke 11y ago
heavenlyhash wants three things: 1) pass structure information around so it can be simulated or reproduced, 2) a deterministic ID for sharing and linking chemical information, and 3) viable methods for determining identity and similarity from the cloud of all chemical configurations. SMILES is better at #1 than InChI, but not as good as a 3D structure representation. But the 3D structure isn't as compact, and offers few advantages for structure identity for small molecules where the 3D configuration is more easily predicted from geometry. InChI is better for #2 than SMILES because different tools generate a different canonical structure, and because general purpose text search engines like Google don't do so well with SMILES as InChI keys. Fingerprints, either binary or count, are more often used for the similarity aspect of #3, than n-gram solutions using the SMILES directly (like LINGO), or any method based on InChI. Also common are 3D shape and electrostatics comparison methods, with attempts to sample configuration space. And for certain chemical structures other approximations are even more important. DNA similarity is based on very different principles than used for small molecules.
- theophrastus 11y ago
  In my humble experience "1)" and "2)" are sufficiently overlapping as to be indistinguishable. Whereas "3)...identity" only demands that the same system be used for both the search compound and the database ("cloud"). For that, a particular implementation of "canonical SMILES" is perfectly respectable. But it's a notably different world once one gets into "3)...similarity". With that you've opened a vast library of doctoral theses, commercial promises, and ingenuity, (and essentially my entire career). And yes, as you suggest, DNA similarity is a wholly different beast.
  - heavenlyhash 11y ago
    Taking dalke's enumeration and running with it... I'd support that "1)" and "2)" are ever so slightly different: defining a serialized form that can reheat to a consistent snapshotted simulation state is one thing; and is necessary but not quite sufficient for "2)". Defining the serialized form to be deterministic is quite an important next step, because that makes a lot of things go from `O(some)` to `O(1)`. Very close, yes. But if we compare to, say, reproducible builds (because it's also dear to my heart), the consequences of that difference are legion. For example: the `tar` command can definitely extract you a filesystem, yes, absolutely. However: whether or not two `tar` implementations (or even the same implementation, run twice in a row) produce the same byte stream is make-or-break for whether someone else can follow your procedure and get the same result. If the process is deterministic, the identity check is cheap: hash it. If the process requires unpacking again to do semantic checks on the contents, the amount of time is... well, if we're hand-waving on the format, essentially unbounded. So... yeah, "canonical SMILES" is a valid answer; that "canonical" part is just really important.
    - dalke 11y ago
      InChI Key is an example of #2 that does not imply #1. For a variation on the theme, if we all agreed on a canonical SMILES method, then the SHA256 of that could be used as a key to connect records, without revealing what the underlying structure is. This is done now, with InChI Key, when two companies want to compare overlap without sharing information about internal compounds. (There was a paper about this last year or so, but I can't find it.) I also pointed out that InChI Keys are better for text-based search engines. As an extreme example, I could produce a line notation which uses only the characters "(", ")", ".", and "-". It would be fine for #1, but poor for #2 for any database search engine which expects some concept of "words" made of letters. This is why I distinguish #1 from #2, even though they are indeed close.
  - dalke 11y ago
    As a structural biochemist, you may have use some of the software I've helped write or contributed to. ;)

dalke 11y ago

heavenlyhash wants three things: 1) pass structure information around so it can be simulated or reproduced, 2) a deterministic ID for sharing and linking chemical information, and 3) viable methods for determining identity and similarity from the cloud of all chemical configurations. SMILES is better at #1 than InChI, but not as good as a 3D structure representation. But the 3D structure isn't as compact, and offers few advantages for structure identity for small molecules where the 3D configuration is more easily predicted from geometry. InChI is better for #2 than SMILES because different tools generate a different canonical structure, and because general purpose text search engines like Google don't do so well with SMILES as InChI keys. Fingerprints, either binary or count, are more often used for the similarity aspect of #3, than n-gram solutions using the SMILES directly (like LINGO), or any method based on InChI. Also common are 3D shape and electrostatics comparison methods, with attempts to sample configuration space. And for certain chemical structures other approximations are even more important. DNA similarity is based on very different principles than used for small molecules.

theophrastus 11y ago
In my humble experience "1)" and "2)" are sufficiently overlapping as to be indistinguishable. Whereas "3)...identity" only demands that the same system be used for both the search compound and the database ("cloud"). For that, a particular implementation of "canonical SMILES" is perfectly respectable. But it's a notably different world once one gets into "3)...similarity". With that you've opened a vast library of doctoral theses, commercial promises, and ingenuity, (and essentially my entire career). And yes, as you suggest, DNA similarity is a wholly different beast.
- heavenlyhash 11y ago
  Taking dalke's enumeration and running with it... I'd support that "1)" and "2)" are ever so slightly different: defining a serialized form that can reheat to a consistent snapshotted simulation state is one thing; and is necessary but not quite sufficient for "2)". Defining the serialized form to be deterministic is quite an important next step, because that makes a lot of things go from `O(some)` to `O(1)`. Very close, yes. But if we compare to, say, reproducible builds (because it's also dear to my heart), the consequences of that difference are legion. For example: the `tar` command can definitely extract you a filesystem, yes, absolutely. However: whether or not two `tar` implementations (or even the same implementation, run twice in a row) produce the same byte stream is make-or-break for whether someone else can follow your procedure and get the same result. If the process is deterministic, the identity check is cheap: hash it. If the process requires unpacking again to do semantic checks on the contents, the amount of time is... well, if we're hand-waving on the format, essentially unbounded. So... yeah, "canonical SMILES" is a valid answer; that "canonical" part is just really important.
  - dalke 11y ago
    InChI Key is an example of #2 that does not imply #1. For a variation on the theme, if we all agreed on a canonical SMILES method, then the SHA256 of that could be used as a key to connect records, without revealing what the underlying structure is. This is done now, with InChI Key, when two companies want to compare overlap without sharing information about internal compounds. (There was a paper about this last year or so, but I can't find it.) I also pointed out that InChI Keys are better for text-based search engines. As an extreme example, I could produce a line notation which uses only the characters "(", ")", ".", and "-". It would be fine for #1, but poor for #2 for any database search engine which expects some concept of "words" made of letters. This is why I distinguish #1 from #2, even though they are indeed close.
- dalke 11y ago
  As a structural biochemist, you may have use some of the software I've helped write or contributed to. ;)