Wednesday, June 26, 2019

The logic of translating chemical knowledge into machine-processable forms: A modern playground for physical-organic chemistry

Karol Molga, Ewa P. Gajewska, Sara Szymkuć, and Bartosz A. Grzybowski (2019)
Highlighted by Jan Jensen
Figure 11 from the paper (c) RSC

This paper offers a, to me, fascinating "look behind the scenes" of Chematica. At the core this program has 75,000 handcrafted reaction rules (SMARTS and Reaction SMARTS strings as shown in the above figure) extracted from the literature (which took over a decade). The authors estimate that there ca 3000-5000 new reaction classes/types appearing in the literature each years and "that there are on the order of 100,000 distinct reaction classes constituting the body of modern organic chemistry. So their work is almost done :).

The paper does a really excellent job of outlining the challenges involved in constructing these rules and present several cases where the rules must be augmented by ML, MM, and Hückel calculations in order to take non-local structural (e.g. strain and steric hindrance) and electronic effects (e.g. on regioselectivity) into account. Such calculations must be done on the millisecond time scale as many thousand intermediates must be inspected during a retrosynthetic search. At the same time they must be very accurate as inaccuracies accumulate with each step on the retrosynthetic path.

It will be very interesting to see if purely ML-based alternatives can beat this approach!


This work is licensed under a Creative Commons Attribution 4.0 International License.

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