Side chain inset of neurogenerative amino acids to metalloproteins: a therapeutic signature for huntingtin protein in Huntington's disease.

OBJECTIVE: Huntington's disease is a dominant autosomal inherited neurodegenerative disease that results in progressive impairment, characterized by dementia, chorea, and behavioral and cognitive decline. The objective of this study was to investigate the potential activity of metalloproteins against the huntingtin protein using various insertion-based engineering computational methods. Metalloproteins, metal protein complexes involved in important biochemical and physiological processes, were explored as potential drug candidates for Huntington's disease. MATERIALS AND METHODS: A total of 18 metalloproteins were selected as drug candidates and studied to assess their potential inhibitory effects on the huntingtin protein. The screening process was based on the lowest binding energy. The metalloprotein with the lowest docking score was chosen for side chain insertion of neurogenerative amino acids. The engineered metalloprotein was then evaluated based on physiochemical properties, allergenicity, toxicity, and surface accessibility. Cloning and expression analysis was performed to further investigate its potential as a therapeutic agent. RESULTS: The metalloprotein chosen for side chain insertion, cytochrome C oxidase, showed promising results. It was computed as a probable non-allergen and exhibited no toxic domains, indicating its non-toxic nature. Additionally, it demonstrated a strong binding affinity with the huntingtin protein, with a binding energy of -1,253.3 Kcal/mol. CONCLUSIONS: Metal-based proteins, when engineered with additional neurogenerative amino acids, hold potential as drug candidates for treating neurodegenerative diseases such as Huntington's disease. The successful development of these engineered metalloproteins could offer therapeutic advantages. Further testing, both in vitro and in vivo, is necessary to evaluate their efficacy and validate their potential activity as novel drugs for the treatment of neurodegenerative diseases.

Halogens engineering-based design of agonists for boosting expression of frataxin protein in Friedreich's ataxia.

OBJECTIVE: Decreased expression of the mitochondrial protein frataxin is the cause of the neurodegenerative disorder Friedreich's ataxia. In patients with cardiac disorders, the death rate of this disease is very high, up to 66%. In order to combat Friedreich ataxia, which is a potentially toxic disorder, de novo drug discovery and design have been created utilizing the approach of compound engineering with halogens. This study aimed to investigate the potential for effective treatment of Friedreich ataxia. MATERIALS AND METHODS: The screening of twenty different agonist compounds was carried out in order to find the most promising agonist compound that may be used for molecular docking prediction against the Frataxin Protein. The compound with the lowest binding energies is then optimized by halogens. The final candidate's drug-like properties are identified through Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profiling. Lipinski's rule of five was checked. Molecular dynamic stimulations were evaluated. RESULTS: The most potent agonist compound was identified out of twenty different compounds utilizing a docking approach against the Frataxin Protein. The compound with the lowest binding energies was next subjected to optimization by halogens. The optimized agonist 9-[1-[(1S, 5R)-8, 8-dimethyl-8-azoniabicyclo[3.2.1]octan-3-yl]triazol-4-yl]fluoren-9-ol  has higher binding energy of -10.4Kcal/mol with molecular weight of 705.63 g/mol. Drug-like properties are identified through ADMET profiling, having water solubility of about -7.59, skin permeation -7.08 cm/s, bioavailability score 0.17, and high GI absorption. The candidate fulfills the Lipinski rule of five and portrays efficient molecular dynamic stimulations. CONCLUSIONS: The selected agonist is one of the most potent compounds in increasing Frataxin protein expression. Furthermore, optimization with halogens can be a productive approach to improve the candidate's drug efficacy. The development of effective medications for the treatment of Friedreich ataxia would be aided by the results of these computational investigations.

Receptor-based screening assays for the detection of antibiotics residues - A review.

Consumer and regulatory agencies have a high concern to antibiotic residues in food producing animals, so appropriate screening assays of fast, sensitive, low cost, and easy sample preparation for the identification of these residues are essential for the food-safety insurance. Great efforts in the development of a high-throughput antibiotic screening assay have been made in recent years. Concerning the screening of antibiotic residue, this review elaborate an overview on the availability, advancement and applicability of antibiotic receptor based screening assays for the safety assessment of antibiotics usage (i.e. radio receptor assay, enzyme labeling assays, colloidal gold receptor assay, enzyme colorimetry assay and biosensor assay). This manuscript also tries to shed a light on the selection, preparation and future perspective of receptor protein for antibiotic residue detection. These assays have been introduced for the screening of numerous food samples. Receptor based screening technology for antibiotic detection has high accuracy. It has been concluded that at the same time, it can detect a class of drugs for certain receptor, and realize the multi-residue detection. These assays offer fast, easy and precise detection of antibiotics.