Improved Method of Structure-Based Virtual Screening via Interaction-Energy-Based Learning.

Virtual screening is a promising method for obtaining novel hit compounds in drug discovery. It aims to enrich potentially active compounds from a large chemical library for further biological experiments. However, the accuracy of current virtual screening methods is insufficient. In this study, we develop a new virtual screening method named Similarity of Interaction Energy VEctor Score (SIEVE-Score), in which protein-ligand interaction energies are extracted to represent docking poses for machine learning. SIEVE-Score offers substantial improvements compared to other state-of-the-art virtual screening methods, namely, other machine-learning-based scoring functions, interaction fingerprints, and docking software, for the enrichment factor 1% results on the Directory of Useful Decoys, Enhanced (DUD-E). The screening results are also human-interpretable in the form of important interactions for distinguishing between active and inactive compounds. The source code is available at https://github.com/sekijima-lab/SIEVE-Score .