Characterizing the potentially neuronal acetylcholinesterase reactivity toward chiral pyraclofos: Enantioselective insights from spectroscopy, in silico docking, molecular dynamics simulation and per-residue energy decomposition studies.

Chiral organophosphorus agents are distributed ubiquitously in the environment, but the neuroactivity of these asymmetric chemicals to humans remains uncertain. This scenario was to explore the stereoselective neurobiological response of human acetylcholinesterase (AChE) to chiral pyraclofos at the enantiomeric scale, and then decipher the microscopic basis of enantioselective neurotoxicity of pyraclofos enantiomers. The results indicated that (R)-/(S)-pyraclofos can form the bioconjugates with AChE with a stoichiometric ratio of 1:1, but the neuronal affinity of (R)-pyraclofos (K = 6.

The anti-alcohol dependency drug disulfiram inhibits the viability and progression of gastric cancer cells by regulating the Wnt and NF-κB pathways.

Objective: Disulfiram is commonly used for alcohol abuse; however, recent studies have revealed its potential as an anti-cancer treatment. This study investigated the effects of disulfiram on gastric cancer and its underlying mechanisms of action.

Methods: The gastric cancer cell lines MKN-45 and SGC-7901 were used for all experiments.

Estimating the potential toxicity of chiral diclofop-methyl: Mechanistic insight into the enantioselective behavior.

Chiral pollutants are widely distributed in the environment; however, the enantioselective toxic effects of these chemicals have still not fully been clarified. Using wet experiments and computational toxicology, this story was to explore the static and dynamic toxic reactions between chiral diclofop-methyl and target protein at the enantiomeric level, and further unveil the microscopic mechanism of enantioselective toxicity of chiral pesticide. Steady-state and time-resolved results indicated that both (R)-/(S)-enantiomers can form the stable toxic conjugates with target protein and the bioaffinities were 1.

Molecular basis for the resistance of American sloughgrass to aryloxyphenoxypropionic acid pesticides and its environmental relevance: A combined experimental and computational study.

Organic pesticides are one of the main environmental pollutants, and how to reduce their environmental risks is an important issue. In this contribution, we disclose the molecular basis for the resistance of American sloughgrass to aryloxyphenoxypropionic acid pesticides using site-directed mutagenesis and molecular modeling and then construct an effective screening model. The results indicated that the target-site mutation (Trp-1999-Leu) in acetyl-coenzyme A carboxylase (ACCase) can affect the effectiveness of the pesticides (clodinafop, fenoxaprop, cyhalofop, and metamifop), and the plant resistance to fenoxaprop, clodinafop, cyhalofop, and metamifop was found to be 564, 19.

Biological effects of α-adrenergic phentolamine on erythrocyte hemeprotein: Molecular insights from biorecognition behavior, protein dynamics and flexibility.

Phentolamine is one of the most representative nonselective α-adrenoreceptor blocking agents, which have been proved to be owned various pharmacological actions. Unfortunately, whether erythrocytes in the veins intervene in biological behaviors of such drug are largely obscured. With the aid of multiple biophysical techniques, this scenario was to detailed explore the potential biorecognition between phentolamine and the hemeprotein in the cytosol of erythrocytes, and the influences of dynamic characters of protein during the bioreaction.

Biophysical exploration of protein-flavonol recognition: effects of molecular properties and conformational flexibility.

The current work explores the biomolecular recognition of a series of flavonols by a protein and then uncovers the influences of the structural features of flavonols and the protein's own characteristics, e.g. the dynamics and flexibility, on the bioavailability of flavonols by using the pivotal biomacromolecule hemoglobin as a model.

Realizing the recognition features of model antipsychotic compounds by important protein: Photochemical and computational studies.

Phenothiazine and its derivatives are the most effective antipsychotic drugs. They have been used in the treatment of serious mental and emotional symptoms including bipolar disorder, organic psychoses, psychotic depression and schizophrenia. However, these drugs cause serious side effects such as akathisia, hyperprolactinaemia and neuroleptic malignant syndrome.

Renal protein reactivity and stability of antibiotic amphenicols: structure and affinity.

In the present work, the molecular recognition of the oldest active amphenicols by the most popular renal carrier, lysozyme, was deciphered by using fluorescence, circular dichroism (CD) and molecular modeling at the molecular scale. Steady state fluorescence data showed that the recognition of amphenicol by lysozyme yields a static type of fluorescence quenching. This corroborates time-resolved fluorescence results that lysozyme-amphenicol adduct formation has a moderate affinity of 10(4) M(-1), and the driving forces were found to be chiefly hydrogen bonds, hydrophobic interactions and π stacking.

Evaluation of the biointeraction of colorant flavazin with human serum albumin: insights from multiple spectroscopic studies, in silico docking and molecular dynamics simulation.

Azo compounds are the largest chemical class of agents frequently used as colorants in a variety of consumer goods and farm produce; therefore, they may become a hazard to public health, because numerous azo compounds and their metabolites are proven to be carcinogens and mutagens. Herein several qualitative and quantitative analytical techniques, including steady state and time-resolved fluorescence, circular dichroism (CD), computer-aided molecular docking as well as molecular dynamics simulation, were employed to ascertain the molecular recognition between the principal vehicle of ligands in human plasma, albumin and a model azo compound, flavazin. The results show that the albumin spatial structure was changed in the presence of flavazin with a decrease of α-helix suggesting partial protein destabilization/self-regulation, as derived from steady state fluorescence, far-UV CD and detailed analyses of three-dimensional fluorescence spectra.

Bioavailability and activity of natural food additive triterpenoids as influenced by protein.

Triterpenoids were thought to be biologically ineffective for a very long time, but aggregating proof on their widely ranging pharmacological activities paired with a dubious toxicity portrait has motivated regenerated attraction for human health and disease. In the current contribution, our central goal was to integratively dissect the biointeraction of two typical triterpenoids, ursolic acid and oleanolic acid, by the most fundamental macromolecule bovine serum albumin (BSA) by employing molecular modeling, steady state and time-resolved fluorescence, and circular dichroism spectra at the molecular scale. Based on molecular modeling, subdomain IIA, which matches Sudlow's site I, was allocated to retain high affinity for triterpenoids, but the affinity of ursolic acid with subdomain IIA is somewhat inferior compared to that of oleanolic acid, probably because the affinity differentiation arises from the different positions of the methyl group on the E-ring in the two triterpenoids.

Binding patterns and structure-affinity relationships of food azo dyes with lysozyme: a multitechnique approach.

Food dyes serve to beguile consumers: they are often used to imitate the presence of healthful, colorful food produce such as fruits and vegetables. But considering the hurtful impact of these chemicals on the human body, it is time to thoroughly uncover the toxicity of these food dyes at the molecular level. In the present contribution, we have examined the molecular reactions of protein lysozyme with model food azo compound Color Index (C.

Molecular recognition of malachite green by hemoglobin and their specific interactions: insights from in silico docking and molecular spectroscopy.

Malachite green is an organic compound that can be widely used as a dyestuff for various materials; it has also emerged as a controversial agent in aquaculture. Since malachite green is proven to be carcinogenic and mutagenic, it may become a hazard to public health. For this reason, it is urgently required to analyze this controversial dye in more detail.