Computer‐aided evaluation and exploration of chemical spaces constrained by reaction pathways
Name
AIChE Journal - 2023 - Levin - Computer‐aided evaluation and exploration of chemical spaces constrained by reaction.pdf
Description
Published version
Size
1.59 MB
Format
Adobe PDF
Checksum (MD5)
5bbae3b1551062a0d8d2c371f405fd55
Author(s)
Levin, Itai
Fortunato, Michael E
Tan, Kian L
Coley, Connor W
Date Issued
December 2023
Journal
AIChE Journal
Publisher
Wiley
Citation
Levin I, Fortunato ME, Tan KL, Coley CW. Computer-aided evaluation and exploration of chemical spaces constrained by reaction pathways. AIChE J. 2023; 69(12):e18234.
Version
Final published version
Abstract
The processes of molecular design and synthetic route selection are necessarily intertwined during discovery. Computational tools have been developed to facilitate synthesis planning, but in a discovery setting, finding a single route to a single molecule of interest may be less important than finding a route that enables rapid access to a library of analogs. Here, we demonstrate how we can estimate route “diversifiability” and use it as a criterion during route selection. We illustrate how the chemical space of synthetically accessible analogs is influenced by properties of alternative starting materials or constraints on their cost. Finally, we integrate these analyses with a synthesizability‐constrained hit expansion workflow in a virtual screening pipeline for focused library expansion around putative hits to support molecular optimization. As medicinal chemistry and adjacent fields shift toward more autonomous design and synthesis of new molecules, it will be increasingly important to embed considerations of synthesizability into molecular design to ensure that computational recommendations are actionable.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Terms of Use
Creative Commons Attribution-Noncommercial-ShareAlike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1002/aic.18234
