Exploring and mapping chemical space with molecular assembly trees

Liu, Y. , Mathis, C., Marshall, S., Bajczyk, M. D., Wilbraham, L. and Cronin, L. (2021) Exploring and mapping chemical space with molecular assembly trees. Science Advances, 7(39), eabj2465. (doi: 10.1126/sciadv.abj2465) (PMID:34559562)

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Abstract

The rule-based search of chemical space can generate an almost infinite number of molecules, but exploration of known molecules as a function of the minimum number of steps needed to build up the target graphs promises to uncover new motifs and transformations. Assembly theory is an approach to compare the intrinsic complexity and properties of molecules by the minimum number of steps needed to build up the target graphs. Here, we apply this approach to prebiotic chemistry, gene sequences, plasticizers, and opiates. This allows us to explore molecules connected to the assembly tree, rather than the entire space of molecules possible. Last, by developing a reassembly method, based on assembly trees, we found that in the case of the opiates, a new set of drug candidates could be generated that would not be accessible via conventional fragment-based drug design, thereby demonstrating how this approach might find application in drug discovery.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mathis, Dr Cole and Liu, Dr Yu and Marshall, Stuart and Cronin, Professor Lee and Wilbraham, Mr Liam
Authors: Liu, Y., Mathis, C., Marshall, S., Bajczyk, M. D., Wilbraham, L., and Cronin, L.
College/School:College of Science and Engineering > School of Chemistry
Journal Name:Science Advances
Publisher:American Association for the Advancement of Science
ISSN:2375-2548
ISSN (Online):2375-2548
Published Online:24 September 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Science Advances 7(39): eabj2465
Publisher Policy:Reproduced under a Creative Commons licence
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