Discovery of novel ULK1 inhibitors through machine learning-guided virtual screening and biological evaluation

Abstract

Aim: Build a virtual screening model for ULK1 inhibitors based on artificial intelligence.Materials & methods: Build machine learning and deep learning classification models and combine molecular docking and biological evaluation to screen ULK1 inhibitors from 13 million compounds. And molecular dynamics was used to explore the binding mechanism of active compounds.Results & conclusion: Possibly due to less available training data, machine learning models significantly outperform deep learning models. Among them, the Naive Bayes model has the best performance. Through virtual screening, we obtained three inhibitors with IC₅₀ of μM level and they all bind well to ULK1. This study provides an efficient virtual screening model and three promising compounds for the study of ULK1 inhibitors.

Keywords: ULK1 inhibitors; drug discovery; machine learning; molecular dynamics simulation; virtual screening.