A Machine Learning-Enabled Pipeline for Large-Scale Virtual Drug Screening

Gupta, Aayush; Zhou, Huan-Xiang

Virtual screening is receiving renewed attention in drug discovery, but progress is hampered by challenges on two fronts: handling the ever increasing sizes of libraries of drug-like compounds, and separating true positives from false positives. Here we developed a machine learning-enabled pipeline for large-scale virtual screening that promises breakthroughs on both fronts. By clustering compounds according to molecular properties and limited docking against a drug target, the full library was trimmed by 10-fold; the remaining compounds were then screened individually by docking; and finally a dense neural network was trained to classify the hits into true and false positives. As illustration, we screened for inhibitors against RPN11, the deubiquitinase subunit of the proteasome and a drug target for breast cancer. TOC Graphic