Virtual screening on the web for drug repurposing: a primer

Abstract

We describe a procedure of performing in silico (virtual) screening using a web-based service, the MTiOpenScreen, which is freely accessible to non-commercial users. We shall use the SARS-CoV-2 main protease as an example. Starting from a structure downloaded from the Protein Data Bank, we discuss how to prepare the coordinates file, taking into account the known biochemical background information of the target protein. The reader will find that this preparation step takes up most of the effort before the target is ready for screening. The steps for uploading the target structure and defining the search volume by critical residues, and the main parameters to use, are outlined. When this protocol is followed, the user will expect to obtain a ranked list of small approved drug compounds docked into the target structure. The results can be readily examined graphically on the web site or downloaded for studying in a local molecular graphics program such as PyMOL.

Keywords: AutoDock Vina; SARS-CoV-2; approved drug; main protease; virtual screening.

Figure 1.

The workflow of the virtual screening procedure using MTiOpenScreen. The middle dark grey boxes are the webpage interfaces where the user interacts with the server. The server side hosts several compound libraries, as well as the screening program AutoDock Vina. On the user side, various activities from supplying input to retrieving output are indicated. The step(s) of this protocol corresponding to each box are indicated.

Figure 2.

The graphical visualizer on the MTiOpenScreen web site. The user can quickly examine the results of the 100 best-docked compounds here. A simple click on the bottom list, which includes the ZINC identifier and the Vina binding energy, will switch to the next ligand. The button corresponding to the active ligand shown is highlighted in green.