A deep learning and docking simulation-based virtual screening strategy enables the rapid identification of HIF-1α pathway activators from a marine natural product database

Abstract

Artificial Intelligence is hailed as a cutting-edge technology for accelerating drug discovery efforts, and our goal was to validate its potential in predicting pharmacological inhibitors of EGLN1 using a deep learning-based architecture, one of its subsidiaries. Egl nine homolog 1 (EGLN1) inhibition prevents poly ubiquitination-mediated proteosomal destruction HIF-1α. The pharmacological interventions aimed at stabilizing HIF-1α have the potential to be a promising treatment option for a range of human diseases, including ischemic stroke. To unveil a novel EGLN1 inhibitor from marine natural products, a custom-based virtual screening was carried out using a Deep Convolutional Neural Network (DCNN) architecture, docking, and molecular dynamics simulation. The custom DCNN model was optimized and further employed to screen marine natural products from the CMNPD database. The docking was performed as a secondary strategy for screened hits. Molecular dynamics (MD) and molecular mechanics/generalized Born surface area (MM-GBSA) were used to analyze inhibitor binding and identify key interactions. The findings support the claim that deep learning-based virtual screening is a rapid, reliable and accurate method of identifying highly contributing drug candidates (EGLN1 inhibitors). This study demonstrates that deep learning architecture can significantly accelerate drug discovery and development, and provides a solid foundation for using (Z)-2-ethylhex-2-enedioic acid [(Z)-2-ethylhex-2-enedioic acid] as a potential EGLN1 inhibitor for treating various health complications.

Communicated by Ramaswamy H. Sarma

Keywords:

• Deep convolutional neural network
• EGLN1
• docking
• molecular dynamics simulation
• hypoxia-inducible factor 1
• ADME
• toxicity
• marine natural products

Disclosure statement

The authors have no conflicts of interest to disclose.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.