Probing the Molecular Basis of Aminoacyl-Adenylate Affinity With Mycobacterium tuberculosis Leucyl-tRNA Synthetase Employing Molecular Dynamics, Umbrella Sampling Simulations and Site-Directed Mutagenesis.

Leucyl-tRNA synthetase (LeuRS) is clinically validated molecular target for antibiotic development. Recently, we have reported several classes of small-molecular inhibitors targeting aminoacyl-adenylate binding site of Mycobacterium tuberculosis LeuRS with antibacterial activity. In this work, we performed in silico site-directed mutagenesis of M.

Identification of novel antistaphylococcal hit compounds.

Staphylococcus aureus is one of the most common nosocomial biofilm-forming pathogens worldwide that has developed resistance mechanisms against majority of the antibiotics. Therefore, the search of novel antistaphylococcal agents with unexploited mechanisms of action, especially with antibiofilm activity, is of great interest. Seryl-tRNA synthetase is recognized as a promising drug target for the development of antibacterials.

Pharmacophore modeling, docking and molecular dynamics simulation for identification of novel human protein kinase C beta (PKCβ) inhibitors.

Unlabelled: Protein kinase Cβ (PKCβ) is considered as an attractive molecular target for the treatment of COVID-19-related acute respiratory distress syndrome (ARDS). Several classes of inhibitors have been already identified. In this article, we developed and validated ligand-based PKCβ pharmacophore models based on the chemical structures of the known inhibitors.

Probing interactions of aminoacyl-adenylate with methionyl-tRNA synthetase through site-directed mutagenesis and free energy calculation.

Methionyl-tRNA synthetase (MetRS) is an attractive molecular target for antibiotic discovery. Recently, we have developed several classes of small-molecular inhibitors of MetRS possessing antibacterial activity. In this article, we performed site-directed mutagenesis of aminoacyl-adenylate binding site of MetRS in order to identify crucial amino acid residues for substrate interaction.

Identification of dual-targeted aminoacyl-tRNA synthetase inhibitors using machine learning.

The most serious challenge in the treatment of tuberculosis is the multidrug resistance of to existing antibiotics. As a strategy to overcome resistance we used a multitarget drug design approach. The purpose of the work was to discover dual-targeted inhibitors of mycobacterial LeuRS and MetRS with machine learning.