Reading The Minds Of Medicinal Chemists

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Includes: ARKG, BBC, BBH, BBP, BIB, BIS, CNCR, FBT, HQL, IBB, LABD, LABS, LABU, PBE, UBIO, XBI, ZBIO
by: Derek Lowe

I suppose that all of us medicinal chemists should be flattered by this press release. According to it:

Medicinal chemistry is among one of the most important and intellectually-challenging professions on the planet. It takes decades of training and experience to learn the properties of the thousands of molecules and their effects on the biological systems, model organisms and diseases. Decisions made by the medicinal chemists affect the lives of billions of people and may result in the billions of dollars of gains or losses for the pharmaceutical companies.

Experienced medicinal chemists have the ability to accurately describe the properties and the possible effects of the molecule just by looking at its structure, as well as at the various numerical parameters.

This was clearly written by distant admirers. Intellectually challenging and important it is, but likely as not it's the folks with "decades of training and experience" who are shown the door. And as for the second paragraph, I wish that we could do that more accurately than we do.

It's true that someone who's been doing this for a while can look at a molecule and say "Looks like a PDE inhibitor/calcium channel blocker/HDAC inhibitor" or what have you, and we can also say things like "Looks insoluble", "Looks like a labile stereocenter", "Looks like it would be cleared fast" or "Someone's tried to fix a metabolic problem by putting that fluorine there". And this is all valuable, and it's valuable for an individual chemist to know these things and to be able to recognize them. But you'll notice that I've hedged all those expressions, because that's all we can do. We can identify what we think is likely, but it's actually the times that we're wrong that are disproportionately more interesting.

That's part of what I was trying to get across when I spoke with Chemjobber for C&E News, that it's easy to sit in the back of a conference room and say "That's not gonna work". You'll be right most of the time, but to what end? It's the times when something really works that we care about, and those are much, much harder to identify. In fact, they're so hard that we generally have no alternative but to run the damn experiments and do all the work.

To get back to that press release, what these folks are proposing to do is, well, read our minds:

Chemistry.AI is a crowd-sourced platform for analyzing the brain's response of medicinal chemists to the molecules developed using artificial intelligence technologies and other expert medicinal chemists. The neuroscientific response is evaluated by analyzing the brain activity of the medicinal chemists using a ubiquitous mobile electroencephalography (EEG) device called EPOC+ produced by EMOTIV. EPOC+ also provides data about head motion and certain facial expressions.

Yeah, I've got some facial expressions they can read - there's one when someone shows me a polyphenolic quinone as a lead screening hit, another one when I'm entering the second hour of an HR presentation, and then there's that one that I make when someone asks me to align the synergies so that the stakeholders have a win/win situation. If I'm any guide, I just hope the software is robust enough to handle what the chemists can throw at it. I can't speak for my EEG readouts, though, and I find it interesting that they're going to that amount of trouble. This would seem to be an attempt at getting to "neurologically revealed preference" as opposed to "stated preference".

But what will they get? The literature on how chemists judge compounds is not particularly encouraging. We're all over the place. We all have our likes and dislikes, based on past experience, and while I applaud the idea of gathering all that experience into one place, I wonder how consistent the result will end up being. If Flannery O'Connor was right that "everything that rises must converge", we may not be rising all that much. So when the founder of this AI effort says that "Medicinal chemists with several years of experience have the ability to distinguish the good molecules from the bad ones just by looking at their structure or its numerical properties and various scores", I worry that we're going to disappoint him severely. If I could distinguish the good molecules from the bad just by looking at them, I would be blogging from my private island fortress rather than the commuter rail train in to work...