An exploration of the binding prediction of anatoxin-a and atropine to acetylcholinesterase enzyme using multi-level computer simulations.

Acetylcholinesterase (AChE) is crucial for the breakdown of acetylcholine to acetate and choline, while the inhibition of AChE by anatoxin-a (ATX-a) results in severe health complications. This study explores the structural characteristics of ATX-a and its interactions with AChE, comparing to the reference molecule atropine for binding mechanisms. Molecular docking simulations reveal strong binding affinity of both ATX-a and atropine to AChE, interacting effectively with specific amino acids in the binding site as potential inhibitors. Quantitative assessment using the MM-PBSA method demonstrates a significantly negative binding free energy of -81.659 kJ mol-1for ATX-a, indicating robust binding, while atropine exhibits a stronger binding affinity with a free energy of -127.565 kJ mol-1. Umbrella sampling calculates the ΔGbindvalues to evaluate binding free energies, showing a favorable ΔGbindof -36.432 kJ mol-1for ATX-a and a slightly lower value of -30.12 kJ mol-1for atropine. This study reveals the dual functionality of ATX-a, acting as both a nicotinic acetylcholine receptor agonist and an AChE inhibitor. Remarkably, stable complexes form between ATX-a and atropine with AChE at its active site, exhibiting remarkable binding free energies. These findings provide valuable insights into the potential use of ATX-a and atropine as promising candidates for modulating AChE activity.

Triazole derived azo-azomethine dye as a new colorimetric anion chemosensor.

In the pursue of developing anion sensors, an efficient triazole derived azo-azomethine dye chemosensor (S) that differentially senses F‾ and AcO‾ ions has been reported. The ions recognition ability of S was investigated by colorimetric and UV-visible spectroscopic methods. Interestingly, this chemosensor molecule is virtually inactive in presence of other anions such as Cl‾, Br‾ and I‾ and HSO4‾. We have further presented a ratiometric approach to differentiate F‾ and AcO‾ ions. The reversibility of F‾ ion binding with S was established by the addition of Ca(NO3)2 to the fluoride bound S, which led to the regeneration of S. The quantum chemical calculation of energies of unbound and bound S has been employed using Density Functional Theory (DFT) to understand the interaction between chemosensor and anions. Evidence in support of fluoride-induced deprotonation of a O-H bond during the detection of F⁻ ion has been demonstrated by employing 1H NMR titration experiments.