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.

Collagen Obtained from Leather Production Waste Provides Suitable Gels for Biomedical Applications.

Collagen and its derivates are typically obtained by extracting them from fresh animal tissues. Lately, however, there has been an increased interest in obtaining collagen from other sources, such as waste material, because of the growing trend to replace synthetic materials with sustainable, natural counterparts in various industries, as well as to ensure a rational waste revalorization. In this paper, collagen was obtained from non-tanned waste of leather production, taken at different stages of the production process: limed pelt, delimed pelt, and fleshings.

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.

Rational Design of Hit Compounds Targeting Threonyl-tRNA Synthetase.

is one of the most dangerous nosocomial pathogens which cause a wide variety of hospital-acquired infectious diseases. is considered as a superbug due to the development of multidrug resistance to all current therapeutic regimens. Therefore, the discovery of antibiotics with novel mechanisms of action to combat staphylococcal infections is of high priority for modern medicinal chemistry.