EViS: An Enhanced Virtual Screening Approach Based on Pocket–Ligand Similarity

Virtual screening (VS) is a popular technology in drug discovery to identify a new scaffold of actives for a specific drug target, which can be classified into ligand-based and structure-based approaches. As the number of protein-ligand complex structures available in public databases increases, it would be possible to develop a template searching-based VS approach that utilizes such information. In this work, we proposed an enhanced VS approach, which is termed EViS, to integrate ligand docking, protein pocket template searching, and ligand template shape similarity calculation. A novel and simple PL-score to characterize local pocket-ligand template similarity was used to evaluate the screening compounds. Benchmark tests were performed on three datasets including DUDE, LIT-PCBA, and DEKOIS. EViS achieved the average enrichment factors (EFs) of 27.8 and 23.4 at a 1% cutoff for experimental and predicted structures on the widely used DUDE dataset, respectively. Detailed data analysis shows that EViS benefits from obtaining favorable ligand poses from docking and using such ligand geometric information to perform three-dimensional (3D) ligand similarity calculations, and the PL-score is efficient to screen compounds based on template searching in the protein-ligand structure database.