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.

Experimental and Theoretical Studies of the HeICl Van der Waals Complexes in the Valence and Ion-pair States.

The article presents results of experimental and theoretical analysis of the T-shaped and linear HeICl van der Waals complexes in the valence A1 and ion-pair β1 states as well as the HeICl(A1,v ,n ←X0 ,v =0,n and β1,v ,n ←A1,v ,n ) optical transitions (n are quantum numbers of the vdW) modes). The HeICl(β1,v ,n )→He+ICl(E0 , , β1) decay are also studied. Luminescence spectra of the HeICl(β1,v =0-3,n ) complex electronic (ICl(E0 ,v , ) and vibrational ICl(β1,v ) predissociation products are measured, and branching ratios of decay channels are determined.

Experimental and theoretical investigation of the ArICl van der Waals complexes in the valence and ion-pair states.

This paper presents the experimental and theoretical analyses of ArICl(IP,v,n) states' population and decay at energies lower than the ArICl(E,v = 0,n) dissociation limit (IP = E0, D'2, β1), v = 0, 1, and n are the quantum numbers of the van der Waals (vdW) modes. We have measured the excitation spectra of the ArICl(E,v = 0,1,n → X,v,n) and ArICl(β,0,n → A and/or D,v ,n →A luminescence as well as luminescence spectra themselves. To construct potential energy surfaces (PESs) for valence (A1, A'2) and ion-pair (E, β, and D') electronic states of the complex, we utilized the intermolecular diatomic-in-molecule perturbation theory first order method.

Identification of novel small-molecular inhibitors of Staphylococcus aureus sortase A using hybrid virtual screening.

Staphylococcus aureus is one of the most dangerous pathogens commonly associated with high levels of morbidity and mortality. Sortase A is considered as a promising molecular target for the development of antistaphylococcal agents. Using hybrid virtual screening approach and FRET analysis, we have identified five compounds able to decrease the activity of sortase A by more than 50% at the concentration of 200 µM.