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Neural Networks for the Prediction of Organic Chemistry Reactions

pubs.acs.org

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Re: Neural Networks for the Prediction of Organic Chemistry Reactions

#11

Post by ghaff »

echelon wrote: post #7
duvenaud wrote: post #3

One of the authors here. Ask us anything! This paper is just a first step - what we'd really like to use this for is designing recipes for synthesizing new molecules. I would also be remiss if I didn't link to a closely-related paper from another group that came out at the same time: http://pubs.acs.org/doi/abs/10.1021/ci5006614

I took three semesters of orgo in undergrad, and if it taught me anything, it's that there are exceptions to nearly every rule. There are so many complicated molecular orbital interactions, requiring years of study. And even then there are always things that break these rules in unexpected ways or produce several products. How do you overcome this? Can you predict yield percentages of each product? What about chirali…

One of the things that I didn't quite get when I started taking organic chemistry was that I really couldn't figure out (didn't have enough background knowledge) why many reactions happened the way they did and that I just had to memorize things.

(Accounting is the same way though for very different reasons. You could justify recording some transactions in about 5 different ways--but FASB says only a particular one is OK.)

Re: Neural Networks for the Prediction of Organic Chemistry Reactions

#12

Post by subnaught »

duvenaud wrote: post #3

One of the authors here. Ask us anything! This paper is just a first step - what we'd really like to use this for is designing recipes for synthesizing new molecules. I would also be remiss if I didn't link to a closely-related paper from another group that came out at the same time: http://pubs.acs.org/doi/abs/10.1021/ci5006614

I am interested as to why you chose to focus on reaction prediction. As you acknowledge in the introduction, the acquistion of this skill is a routine part of graduate education in synthetic chemistry.

On the other hand, the key difficulty in synthetic chemistry, and the one that occupies the majority of a chemist's time is the identification of the correct reagent(s), the correct solvent, and the correct time, temperature, and concentration such that the desired reaction proceeds in a convenient amount of time and with the correct chemo- and regio-selectivity, that the reaction conditions are tolerated by the rest of the molecule, and that the product can be easily isolated from the reaction byproducts.

In my opinion, as long as these problems remain, then being able to turn retrosynthetic analysis over to a machine appears to me to provide little benefit.

Re: Neural Networks for the Prediction of Organic Chemistry Reactions

#13

Post by peaceb »

duvenaud wrote: post #3

One of the authors here. Ask us anything! This paper is just a first step - what we'd really like to use this for is designing recipes for synthesizing new molecules. I would also be remiss if I didn't link to a closely-related paper from another group that came out at the same time: http://pubs.acs.org/doi/abs/10.1021/ci5006614

First of all, interesting and fascinating work! It is nice to see some chemistry over here.

I'm a grad student in computational chemistry. I am fascinated by the idea that our imagination, or limits of our chemical intuition, is the limiting factor for all kinds of cool advances. Through that I have recently been studying machine learning and I am interested in using it for catalyst optimization and design.

What is your opinion on the state of computationally assisted inverse design of molecules and the role of machine learning in it? The problem is a bit more open-ended compared to reaction optimization, but I could imagine that after proper formulation of the design guidelines the computer could help a lot.

Re: Neural Networks for the Prediction of Organic Chemistry Reactions

#14

Post by wuschel »

Very interesting, great concept! The paper is on my to-read list!

I am only afraid that the datasets you have used might not be of sufficiently quality for a neural network application. There are old recipes when the state of art in chemistry was at an earlier stage e.g. before the discovery of specific mechanisms, molecule classes, analytics and general concepts. Also, as mentioned in this thread, there are aspects of the synthetic chemists work and experience that might not be taken into consideration in this approach.

Re: Neural Networks for the Prediction of Organic Chemistry Reactions

#15

Post by duvenaud »

subnaught wrote: post #12
duvenaud wrote: post #3

One of the authors here. Ask us anything! This paper is just a first step - what we'd really like to use this for is designing recipes for synthesizing new molecules. I would also be remiss if I didn't link to a closely-related paper from another group that came out at the same time: http://pubs.acs.org/doi/abs/10.1021/ci5006614

I am interested as to why you chose to focus on reaction prediction. As you acknowledge in the introduction, the acquistion of this skill is a routine part of graduate education in synthetic chemistry. On the other hand, the key difficulty in synthetic chemistry, and the one that occupies the majority of a chemist's time is the identification of the correct reagent(s), the correct solvent, and the correct time, tempe…

Good points. However, even if chemists already know how to predict reactions, giving this knowledge to a machine will allow a much faster search over possible synthetic routes.

I agree that reaction outcomes depend on many other factors besides the reagents. In the future, I'm sure we'll create reaction prediction frameworks that also take these other factors as inputs. The problem right now is that there aren't many datasets that include these extra factors.

We're not advocating turning retrosynthetic analysis over to machines yet. These are just baby steps.

Re: Neural Networks for the Prediction of Organic Chemistry Reactions

#17

Post by pama »

duvenaud wrote: post #15
subnaught wrote: post #12

Earlier quoted context omitted.

I am interested as to why you chose to focus on reaction prediction. As you acknowledge in the introduction, the acquistion of this skill is a routine part of graduate education in synthetic chemistry. On the other hand, the key difficulty in synthetic chemistry, and the one that occupies the majority of a chemist's time is the identification of the correct reagent(s), the correct solvent, and the correct time, tempe…

Good points. However, even if chemists already know how to predict reactions, giving this knowledge to a machine will allow a much faster search over possible synthetic routes. I agree that reaction outcomes depend on many other factors besides the reagents. In the future, I'm sure we'll create reaction prediction frameworks that also take these other factors as inputs. The problem right now is that there aren't many…

Did you consider working with a chemistry CRO (say WuXi) to train models using their proprietary datasets? Is there some solution that's a win-win for everyone?

Re: Neural Networks for the Prediction of Organic Chemistry Reactions

#18

Post by duvenaud »

echelon wrote: post #7
duvenaud wrote: post #3

One of the authors here. Ask us anything! This paper is just a first step - what we'd really like to use this for is designing recipes for synthesizing new molecules. I would also be remiss if I didn't link to a closely-related paper from another group that came out at the same time: http://pubs.acs.org/doi/abs/10.1021/ci5006614

I took three semesters of orgo in undergrad, and if it taught me anything, it's that there are exceptions to nearly every rule. There are so many complicated molecular orbital interactions, requiring years of study. And even then there are always things that break these rules in unexpected ways or produce several products. How do you overcome this? Can you predict yield percentages of each product? What about chirali…

Thanks for the kind words! I would agree that the function we're trying to learn is very complicated, with many exceptions. But that only improves our comparative advantage, at least compared to novice chemists. We might also be able to help our system take advantage of the knowledge of physics that expert chemists use to predict reaction outcomes by giving our network access to the output of a physical reaction simulator.

Extending the system to (try to) predict yield percentages or chirality is straightforward. The hard part, in my mind, is that there aren't a fixed number of reaction types. As molecules get bigger, we'll have to move away from predicting one of a fixed set of reaction types, to directly predicting products - but this is a much harder problem.

Our system probably isn't good enough to design synthesis pathways yet, but that is the eventual goal. A system that also predicted yield would of course help with that, and that would be another straightforward extension.

Re: Neural Networks for the Prediction of Organic Chemistry Reactions

#19

Post by duvenaud »

peaceb wrote: post #13
duvenaud wrote: post #3

One of the authors here. Ask us anything! This paper is just a first step - what we'd really like to use this for is designing recipes for synthesizing new molecules. I would also be remiss if I didn't link to a closely-related paper from another group that came out at the same time: http://pubs.acs.org/doi/abs/10.1021/ci5006614

First of all, interesting and fascinating work! It is nice to see some chemistry over here. I'm a grad student in computational chemistry. I am fascinated by the idea that our imagination, or limits of our chemical intuition, is the limiting factor for all kinds of cool advances. Through that I have recently been studying machine learning and I am interested in using it for catalyst optimization and design. What is y…

Thank you! I guess all you need to do to get chemistry on hacker news is add neural nets to it.

I honestly don't know much about synthesis or the state of computationally assisted inverse design of molecules, except that it seems like a great idea, and that it is still early days. As you say, proper formulation of the guidelines is still necessary - as far as I understand, right now the synthesis people still use a lot of judgement at each step, and all these little choices will have to be recorded to build a useful dataset.

Re: Neural Networks for the Prediction of Organic Chemistry Reactions

#20

Post by duvenaud »

wuschel wrote: post #14

Very interesting, great concept! The paper is on my to-read list! I am only afraid that the datasets you have used might not be of sufficiently quality for a neural network application. There are old recipes when the state of art in chemistry was at an earlier stage e.g. before the discovery of specific mechanisms, molecule classes, analytics and general concepts. Also, as mentioned in this thread, there are aspects…

Yes, the datasets were the real limiting factor for this project, and as you point out, reactions depend on many more things than their reagents. Hopefully this work will inspire someone to build a better dataset of reaction setups and outcomes!
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