Docking-Based Virtual Screening for the Discovery of 1,3,4-Oxadiazoles as Aminoacyl-tRNA Synthetase Inhibitors

Abstract

Aminoacyl-tRNA synthetases (aaRSs) are one of the leading targets for the development of antibiotic agents. In this paper, we reported the discovery of aaRS inhibitors using a structure-based virtual screening method. The interactions of 52 designed structures with the methionyl-tRNA synthetase (MetRS) target were performed by docking the ligands into the active zone of the MetRS using Autodock Vina. The data revealed 14 compounds displaying interactions with key amino acids (Asp287, Tyr250, Val473, Trp474, Phe522, Ile519, Ala477, Leu478, and His523) at the binding pocket of the enzyme, indicating their potential as MetRS inhibitors. These results could be served as the references for further synthetic work and bioassays experiments for discovering MetRS inhibitors and other pharmaceutical agents that may assist in the generation of new antibiotics.

Computational Identification of Methionyl-tRNA-Synthetase Inhibitors for Brucella melitensis: A Hybrid of Ligand-based Classic 3-Point Pharmacophore Screening and Structure Cavity Guided Blind Docking Approach

“…This research paper focuses on the computational identification of methionyl-tRNA synthetase inhibitors specific to B. melitensis using a ligand-based approach, with a particular emphasis on the classic 3-point pharmacophore screening method. 5 The ligand-based approach leverages the knowledge of known bioactive compounds to predict and prioritize potential inhibitors based on structural and chemical similarities. The classic 3-point pharmacophore screening method, a robust and widely employed technique, further refines the selection process by considering key features essential for ligand binding and biological activity.…”