<html><head><meta http-equiv="Content-Type" content="text/html; charset=utf-8"></head><body style="word-wrap: break-word; -webkit-nbsp-mode: space; line-break: after-white-space;" class="">Would this be of any use?<div class=""><br class=""></div><div class=""><a href="https://www.molgen.de/" class="">https://www.molgen.de/</a></div><div class=""><br class=""></div><div class="">It sounded like you were doing something that you want to be fast and in-line, and I don’t know if MOLGEN grants an API that offers that degree of flexibility. People I know who have worked with it say that it is fairly sophisticated in creating physically realizable molecules while still retaining as much combinatorics as possible. </div><div class=""><br class=""></div><div class="">Eric</div><div class=""><br class=""></div><div class=""><br class=""><div><br class=""><blockquote type="cite" class=""><div class="">On Oct 13, 2021, at 1:17 AM, Roger Critchlow <<a href="mailto:rec@elf.org" class="">rec@elf.org</a>> wrote:</div><br class="Apple-interchange-newline"><div class=""><div dir="ltr" class=""><div dir="ltr" class="">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.</div><div dir="ltr" class=""><br class=""></div><div dir="ltr" class="">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.</div><div dir="ltr" class=""><br class=""></div><div class="">OpenEyes (<a href="https://linkprotect.cudasvc.com/url?a=https%3a%2f%2fwww.eyesopen.com%2f&c=E,1,_xhq5QreQZB85pzOZP4KFzWNyfJ6g58Ug0kZ0JhX8dk_Swwzs3vVfH3NzcPCYAmGXnfJwwPGIy92mvg8xwUamvtMznmqiBwYIVKPMrP9mxu0PNYU1yT1CA,,&typo=1" class="">https://www.eyesopen.com/</a>) is running some online events this month that might be interesting.</div><div class=""><br class=""></div><div class="">-- rec --</div><div class=""><br class=""></div><div class="gmail_quote"><div dir="ltr" class="gmail_attr">On Tue, Oct 12, 2021 at 5:44 PM Marcus Daniels <<a href="mailto:marcus@snoutfarm.com" target="_blank" class="">marcus@snoutfarm.com</a>> wrote:<br class=""></div><blockquote class="gmail_quote" style="margin:0px 0px 0px 0.8ex;border-left:1px solid rgb(204,204,204);padding-left:1ex">
<div lang="EN-US" class="">
<div class=""><p class="MsoNormal">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). <u class=""></u><u class=""></u></p><p class="MsoNormal"><u class=""></u> <u class=""></u></p><p class="MsoNormal">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.<u class=""></u><u class=""></u></p><p class="MsoNormal"><u class=""></u> <u class=""></u></p>
<div style="border-right:none;border-bottom:none;border-left:none;border-top:1pt solid rgb(225,225,225);padding:3pt 0in 0in" class=""><p class="MsoNormal"><b class="">From:</b> Friam <<a href="mailto:friam-bounces@redfish.com" target="_blank" class="">friam-bounces@redfish.com</a>> <b class="">On Behalf Of
</b>Roger Critchlow<br class="">
<b class="">Sent:</b> Tuesday, October 12, 2021 2:10 PM<br class="">
<b class="">To:</b> The Friday Morning Applied Complexity Coffee Group <<a href="mailto:friam@redfish.com" target="_blank" class="">friam@redfish.com</a>><br class="">
<b class="">Subject:</b> Re: [FRIAM] Schwill Rock?<u class=""></u><u class=""></u></p>
</div><p class="MsoNormal"><u class=""></u> <u class=""></u></p>
<div class="">
<div class=""><p class="MsoNormal">Hmm, when I was in the drug discovery canal, the "descriptors" that you could calculate from a SMILES string were legion. <u class=""></u><u class=""></u></p>
<div class=""><p class="MsoNormal"><u class=""></u> <u class=""></u></p>
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<div class=""><p class="MsoNormal">Here's the list for RDKIT, <a href="https://linkprotect.cudasvc.com/url?a=https%3a%2f%2fwww.rdkit.org%2fdocs%2fGettingStartedInPython.html%23list-of-available-descriptors&c=E,1,_kV11Wpf_w1jT9C6j7k5J6CtV07T8ZMZLuU_TZVTdAv25WVN3Yk22udDwGD8Ti62gmCqg8x92QOM2UkL6j7n_2jsDLSzmxBHU6BMX2kShuNUW0_oZg,,&typo=1" target="_blank" class="">https://www.rdkit.org/docs/GettingStartedInPython.html#list-of-available-descriptors</a>. 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.<u class=""></u><u class=""></u></p>
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<div class=""><p class="MsoNormal"><u class=""></u> <u class=""></u></p>
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<div class=""><p class="MsoNormal">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.<u class=""></u><u class=""></u></p>
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<div class=""><p class="MsoNormal"><u class=""></u> <u class=""></u></p>
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<div class=""><p class="MsoNormal">-- rec --<u class=""></u><u class=""></u></p>
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<div class=""><p class="MsoNormal"><u class=""></u> <u class=""></u></p>
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<div class=""><p class="MsoNormal">On Tue, Oct 12, 2021 at 3:22 PM Marcus Daniels <<a href="mailto:marcus@snoutfarm.com" target="_blank" class="">marcus@snoutfarm.com</a>> wrote:<u class=""></u><u class=""></u></p>
</div>
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<blockquote style="border-top:none;border-right:none;border-bottom:none;border-left:1pt solid rgb(204,204,204);padding:0in 0in 0in 6pt;margin-left:4.8pt;margin-right:0in" class="">
<div class="">
<div class=""><p class="MsoNormal">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.<u class=""></u><u class=""></u></p><p class="MsoNormal"> <u class=""></u><u class=""></u></p>
<div style="border-right:none;border-bottom:none;border-left:none;border-top:1pt solid rgb(225,225,225);padding:3pt 0in 0in" class=""><p class="MsoNormal"><b class="">From:</b> Friam <<a href="mailto:friam-bounces@redfish.com" target="_blank" class="">friam-bounces@redfish.com</a>>
<b class="">On Behalf Of </b>Jon Zingale<br class="">
<b class="">Sent:</b> Tuesday, October 12, 2021 12:11 PM<br class="">
<b class="">To:</b> <a href="mailto:friam@redfish.com" target="_blank" class="">friam@redfish.com</a><br class="">
<b class="">Subject:</b> Re: [FRIAM] Schwill Rock?<u class=""></u><u class=""></u></p>
</div><p class="MsoNormal"> <u class=""></u><u class=""></u></p>
<div class="">
<div class=""><p class="MsoNormal"><span style="font-size:12pt;font-family:Verdana,sans-serif;color:rgb(51,51,51)" class="">"</span><span style="font-size: 12pt; font-family: Arial, sans-serif;" class="">I mean from the perspective
of aesthetics. Understanding why Pandora is messing it up means sampling the deep wells."</span><u class=""></u><u class=""></u></p>
</div>
<div class=""><p class="MsoNormal"><span style="font-size:12pt;font-family:Verdana,sans-serif;color:rgb(51,51,51)" class=""> </span><u class=""></u><u class=""></u></p>
</div>
<div class=""><p class="MsoNormal"><span style="font-size: 12pt; font-family: Arial, sans-serif;" class="">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.</span><u class=""></u><u class=""></u></p>
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