Docking-Based Virtual Screening Using PyRx Tool: Autophagy Target Vps34 as a Case Study

Virtual screening (VS) is a computational approach used to screen a large number of database molecules to identify leads. It decreases both the time and resources required to test the whole database experimentally, by selecting only the most promising ones. Docking-based virtual screening (DBVS) methods explore the behavior of small molecules in the binding pocket of targets, to select the best interacting molecules for testing experimentally. Several docking programs/software have been developed to perform DBVS of large databases. This chapter describes the use of one such open-access tool PyRx 0.8 (https://pyrx.sourceforge.io/; https://sourceforge.net/projects/pyrx/), which is user-friendly and can run on many operating systems. This tool combines several open-source software, including AutoDock, AutoDock Vina, and Open Babel to carry out DBVS seamlessly. We demonstrate in a step-by-step manner the use of the PyRx tool to perform DBVS of database compounds for autophagy target Vps34 (vacuolar protein sorting 34), to identify potential molecules for testing in the lab. Overall, this chapter provides an easy understanding and systematic protocol to use the PyRx tool for carrying out DBVS, with a case study.