Entangled Conditional Adversarial Autoencoder for de Novo Drug Discovery

被引:180
作者
Polykovskiy, Daniil [1 ,2 ]
Zhebrak, Alexander [1 ]
Vetrov, Dmitry [2 ]
Ivanenkov, Yan [1 ,4 ,5 ]
Aladinskiy, Vladimir [1 ,5 ]
Mamoshina, Polina [1 ]
Bozdaganyan, Marine [1 ]
Aliper, Alexander [1 ]
Zhavoronkov, Alex [1 ]
Kadurin, Artur [1 ,3 ]
机构
[1] Insilico Med, Rockville, MD 20850 USA
[2] Natl Res Univ, Higher Sch Econ, Moscow 101000, Russia
[3] Insilico Taiwan, Taipei 115, Taiwan
[4] Russian Acad Sci, Inst Biochem & Genet, Ufa 450054, Russia
[5] State Univ, Moscow Inst Phys & Technol, Dolgoprudnyi 141700, Moscow Region, Russia
基金
俄罗斯科学基金会;
关键词
adversarial autoencoders; disentanglement; conditional generation; Janus kinase; DESIGN; GENERATION; INHIBITORS; ALGORITHM; SMILES;
D O I
10.1021/acs.molpharmaceut.8b00839
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Modern computational approaches and machine learning techniques accelerate the invention of new drugs. Generative models can discover novel molecular structures within hours, while conventional drug discovery pipelines require months of work. In this article, we propose a new generative architecture, entangled conditional adversarial autoencoder, that generates molecular structures based on various properties, such as activity against a specific protein, solubility, or ease of synthesis. We apply the proposed model to generate a novel inhibitor of Janus kinase 3, implicated in rheumatoid arthritis, psoriasis, and vitiligo. The discovered molecule was tested in vitro and showed good activity and selectivity.
引用
收藏
页码:4398 / 4405
页数:8
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