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Issue 4, 2020
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Scaffold-based molecular design with a graph generative model

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Abstract

Searching for new molecules in areas like drug discovery often starts from the core structures of known molecules. Such a method has called for a strategy of designing derivative compounds retaining a particular scaffold as a substructure. On this account, our present work proposes a graph generative model that targets its use in scaffold-based molecular design. Our model accepts a molecular scaffold as input and extends it by sequentially adding atoms and bonds. The generated molecules are then guaranteed to contain the scaffold with certainty, and their properties can be controlled by conditioning the generation process on desired properties. The learned rule of extending molecules can well generalize to arbitrary kinds of scaffolds, including those unseen during learning. In the conditional generation of molecules, our model can simultaneously control multiple chemical properties despite the search space constrained by fixing the substructure. As a demonstration, we applied our model to designing inhibitors of the epidermal growth factor receptor and show that our model can employ a simple semi-supervised extension to broaden its applicability to situations where only a small amount of data is available.

Graphical abstract: Scaffold-based molecular design with a graph generative model

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Supplementary files

Article information


Submitted
06 Sep 2019
Accepted
03 Dec 2019
First published
03 Dec 2019

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2020,11, 1153-1164
Article type
Edge Article

Scaffold-based molecular design with a graph generative model

J. Lim, S. Hwang, S. Moon, S. Kim and W. Y. Kim, Chem. Sci., 2020, 11, 1153
DOI: 10.1039/C9SC04503A

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material and it is not used for commercial purposes.

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    [Original citation] - Published by The Royal Society of Chemistry.

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