Entangled Conditional Adversarial Autoencoder for de Novo Drug Discovery.

Journal: Molecular pharmaceutics
Published Date:

Abstract

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.

Authors

  • Daniil Polykovskiy
    Insilico Medicine , Baltimore , Maryland 21218 , United States.
  • Alexander Zhebrak
    Pharmaceutical Artificial Intelligence Department, Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern, Baltimore, Maryland, USA.
  • Dmitry Vetrov
    National Research University Higher School of Economics , Moscow 101000 , Russia.
  • Yan Ivanenkov
    Pharma.AI Department , Insilico Medicine, Inc. , Baltimore , Maryland 21218 , United States.
  • Vladimir Aladinskiy
    Pharma.AI Department , Insilico Medicine, Inc , Baltimore , Maryland 21218 , United States.
  • Polina Mamoshina
    Pharmaceutical Artificial Intelligence Department, Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern, Baltimore, Maryland, USA.
  • Marine Bozdaganyan
    Insilico Medicine , Rockville , Maryland 20850 , United States.
  • Alexander Aliper
    Pharmaceutical Artificial Intelligence Department, Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern, Baltimore, Maryland, USA.
  • Alex Zhavoronkov
    Pharmaceutical Artificial Intelligence Department, Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern, Baltimore, Maryland, USA.
  • Artur Kadurin
    Search Department, Mail.Ru Group Ltd., Moscow, Russia.