[FRIAM] Schwill Rock?

[Roger Critchlow]

As long as you stick to basic CNO type chemistry, you can probably figure
out a valid SMILES generator pretty quickly.  But it might be easier to
work in the explicit molecule graph instead and just use SMILES as a
content name string.  The things that might go wrong after the SMILES input
parses correctly are 1) a ring that's strained because it's too tight a
turn, 2) steric hindrance between bulky sidechains occupying the same
space, and 3) something that no one has any idea how to make.  You could
probably notice 1) and 2) if you track the average energy per bond.

The benzodiazepines are a classic example of structuring the search around
a core framework and substituting side chains onto the core.  That's the
way the chemists do it in the wetlab.

OpenEyes (https://www.eyesopen.com/) is running some online events this
month that might be interesting.

-- rec --

On Tue, Oct 12, 2021 at 5:44 PM Marcus Daniels <marcus at snoutfarm.com> wrote:

> A search algorithm that, say, proposes a prefix or a suffix to a SMILES
> string would need to have a way to autocomplete candidates before it could
> use these descriptors to guide an optimization because the parsing step is
> non-trivial, never mind the sanitization step (mentioned on that web
> page).
>
>
>
> I will deflect blame on Jon for changing the topic from music to
> chemicals, but presumably with enough debate their aesthetic preferences in
> music could be formalized in theory or some rule-based way, as is manifest
> here.
>
>
>
> *From:* Friam <friam-bounces at redfish.com> *On Behalf Of *Roger Critchlow
> *Sent:* Tuesday, October 12, 2021 2:10 PM
> *To:* The Friday Morning Applied Complexity Coffee Group <
> friam at redfish.com>
> *Subject:* Re: [FRIAM] Schwill Rock?
>
>
>
> Hmm, when I was in the drug discovery canal, the "descriptors" that you
> could calculate from a SMILES string were legion.
>
>
>
> Here's the list for RDKIT,
> https://www.rdkit.org/docs/GettingStartedInPython.html#list-of-available-descriptors.
> There are one bunch that depend entirely on the formula and molecular
> structure.  Then there's a whole other bunch you can compute if you
> generate 3d structures for the molecules, possibly multiplied by the number
> of low energy structures the molecule can adopt.
>
>
>
> What kind of plausibility were you looking for?  Does the SMILES string
> specify a real molecule?  That's hard.  There are syntax errors in SMILES,
> failures to close rings, valency errors, charge errors.  But there are lots
> of syntactically valid SMILES that won't match any known molecule, either
> because they're impossible or as yet to be determined.  The pharmas all
> have their own lists of molecules of interest, but those are proprietary.
> Looks like there are various online databases, none that I'm familiar
> with.  If the SMILES parses, you can try generating a 2d depiction and a 3d
> structure.  Those will throw exceptions if things get too weird.
>
>
>
> -- rec --
>
>
>
> On Tue, Oct 12, 2021 at 3:22 PM Marcus Daniels <marcus at snoutfarm.com>
> wrote:
>
> I was playing with RDKIT the other day, and it wasn’t obvious how to get a
> scalar quantity of plausibility of a molecule.   It seems a SMILES string
> is right or wrong, and then maybe there are some warnings that can be
> trapped.   However, the benefits for search or fair sampling are different
> than the needs of correctness checks, which is deeper property.   That
> isn’t quite a fit to the music example where aesthetic considerations are
> subjective.
>
>
>
> *From:* Friam <friam-bounces at redfish.com> *On Behalf Of *Jon Zingale
> *Sent:* Tuesday, October 12, 2021 12:11 PM
> *To:* friam at redfish.com
> *Subject:* Re: [FRIAM] Schwill Rock?
>
>
>
> "I mean from the perspective of aesthetics. Understanding why Pandora is
> messing it up means sampling the deep wells."
>
>
>
> Yes, but not more than one has to. This is why I am advocating for methods
> like a weighted ensemble. The working analogy for me comes from drug
> discovery. It doesn't make a lot of sense to probe the same old sites and
> the same old conformations.
>
>
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