Analysis of Bacillus anthracis nucleoside hydrolase via in silico docking with inhibitors and molecular dynamics simulation

Abstract

As the enzyme nucleoside hydrolase (NH) is widely found in nature but has not yet been detected in mammals, it is considered an ideal target in the development of chemotherapy against parasitic diseases and bacterial infections like anthrax. Considering the risk that this biological warfare agent represents nowadays, the search for new drugs and new molecular targets in the development of chemotherapy against anthrax is imperative. On this basis, we performed docking studies of six known NH inhibitors at the active site of NH from Bacillus anthracis (BaNH). Subsequently, molecular dynamics (MD) simulations of these compounds inside BaNH were carried out in order to complement the docking studies and select the most promising compounds as leads for the design of potential BaNH inhibitors. Most of the docking and MD results obtained agreed well with each other and showed good correlation with experimental data.

Screening and Characterization of Purine Nucleoside Degrading Lactic Acid Bacteria Isolated from Chinese Sauerkraut and Evaluation of the Serum Uric Acid Lowering Effect in Hyperuricemic Rats

“…These nucleosidases are widely found in plants and microorganisms but have not yet been detected in mammals [36]. Nucleoside hydrolases break the β-glycoside bonds of nucleosides and release nitrogenous bases and pentose.…”

Structural basis ofBacillus anthracisMoxXT disruption and the modulation of MoxT ribonuclease activity by rationally designed peptides

“…Disruption of TA interaction and artificial toxin activation has been proposed as a strategy for development of antibacterial molecules in TA systems but may cause persister cell formation (Williams & Hergenrother, 2012). Other novel molecules have also been proposed as novel and selective targets for development of antimicrobial therapeutics in B. anthracis (Beierlein & Anderson, 2011;Guimaraes, Oliveira, da Cunha, Ramalho, & Franca, 2011). Designed peptides have previously been tested for TA disruption in the ε-ζ TA interaction in Streptococcus pyogenes.…”

New in silico insights into the application of the (hydroxy)chloroquine with macrolide antibiotics co-crystals against the SARS-CoV-2 virus

“…The compounds were then docked inside the crystallographic structure of viral protein M pro (PDB code 6LU7; resolution = 2.16 Å), [25] using the Molegro Virtual Docker program (MVD®), [26] taking into account the same procedures employed previously. [27][28][29] According to our calculation protocol, it was considered a radius of about 20 Å, where the residues of the catalytic triad were kept as exible. Due to the nature of the docking methods, the calculations were carried out, generating approximately 50 poses (hence such as conformation and orientation) for each ligand studied.…”