This work introduces a method to tune a sequence-based generative model for
molecular de novo design that through augmented episodic likelihood can learn
to generate structures with certain specified desirable properties. We
demonstrate how this model can execute a range of tasks such as generating
analogues to a query structure and generating compounds predicted to be active
against a biological target. As a proof of principle, the model is first
trained to generate molecules that do not contain sulphur. As a second example,
the model is trained to generate analogues to the drug Celecoxib, a technique
that could be used for scaffold hopping or library expansion starting from a
single molecule. Finally, when tuning the model towards generating compounds
predicted to be active against the dopamine receptor type 2, the model
generates structures of which more than 95% are predicted to be active,
including experimentally confirmed actives that have not been included in
either the generative model nor the activity prediction model.

本文介绍了一种基于序列的生成模型来设计分子的方法，通过增强情节似然性可以学习生成具有某些指定的理想特性的结构。将模型应用于生成类似物质结构，生成与药物 Celecoxib 类似的分子以及具有活性的化合物。最后，将模型调整为生成预测对多巴胺受体 2 具有活性的化合物，得到了 95% 以上的预测为活性的结构，其中包括实验证实的活性化合物。