Deep Learning Predicts Protein-Ligand Interactions

This paper presents results from a rapid-response industry-academia collaboration for virtual screening of chemical, natural and virtual drug ligands towards identifying potential therapeutics for COVID-19. Compared to resource-intensive traditional approaches of either conducting hight-hroughput screening in a lab or in-silico molecular dynamics simulations on supercomputers, we have developed an open-source framework that leverages artificial intelligence (AI) to accurately and quickly predict the binding potential of a drug ligand with a target protein. We have trained a novel molecular-highway graph neural network architecture using the entirety of the BindingDB database to predict the probability of a drug ligand binding to a protein target. Our approach achieves a prodigious 98.3% accuracy with its predictions. Through this paper, we disseminate our source code and use the AI model to screen both public (ChEMBL, DrugBank) and proprietary databases. Compared to other AI-based methods, our approach outperforms the state-of-the-art on the following metrics - (i) number of molecules currently undergoing active clinical trials, (ii) number of antiviral drugs correctly identified, (iii) accuracy despite not needing active-site priors, and (iv) ability to screen more compounds in unit time.YYYY