Calcium homeostasis modulator 1 (CALHM1) is a protein responsible for causing Alzheimer's disease. In the absence of an experimentally designed protein molecule, homology modelling was performed. Through homology modelling, different CALHM1 models were generated and validated through Rampage. To carry out further in silico studies, through molecular docking and molecular dynamics simulation experiments, various flavonoids and alkaloids from were utilised as inhibitors to target the protein (CALHM1). The sequence of CALHM1 was retrieved from UniProt and the secondary structure prediction of CALHM1 was done through CFSSP, GOR4, and SOPMA methods. The structure was identified through LOMETS, MUSTER, and MODELLER and finally, the structures were validated through Rampage. plant was used to check the interaction of alkaloids and flavonoids against CALHM1. The protein and protein-ligand complex were also validated through molecular dynamics simulations studies. The model generated through MODELLER software with 6VAM A was used because this model predicted the best results in the Ramachandran plot. Further molecular docking was performed, quercetin was found to be the most appropriate candidate for the protein molecule with the minimum binding energy of -12.45 kcal/mol and their ADME properties were analysed through Molsoft and Molinspiration. Molecular dynamics simulations showed that CALHM1 and CALHM1-quercetin complex became stable at 2500 ps. It may be seen through the study that quercetin may act as a good inhibitor for treatment. With the help of an in silico study, it was easier to analyse the 3D structure of the protein, which may be scrutinized for the best-predicted model. Quercetin may work as a good inhibitor for treating Alzheimer's disease, according to in silico research using molecular docking and molecular dynamics simulations, and future in vitro and in vivo analysis may confirm its effectiveness.
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http://dx.doi.org/10.3390/brainsci12060770 | DOI Listing |
J Phys Chem B
December 2024
School of Energy and Power Engineering, Northeast Electric Power University, Jilin 132012, China.
When water is confined in a nanochannel, its thermodynamic and kinetic properties change dramatically compared to the macroscale. To investigate these phenomena, we conducted nonequilibrium molecular dynamics simulations on the heat transfer in copper-water nanochannels with lengths ranging from 12 to 20 nm in the absence and presence of an electric field. The results indicate that in the absence of an electric field ( = 12-20 nm), the binding force between water molecules in the 20 nm nanochannel is the weakest, facilitating thermal motion in the liquid phase.
View Article and Find Full Text PDFChem Biodivers
December 2024
Noakhali Science and Technology University, Microbiology, Sonapur, Noakhali, BANGLADESH.
Cryptococcus neoformans, the most opportunistic fungal pathogen, causes cryptococcal meningitis. Based on molecular docking and ADME/toxicity analysis, the top two lead compounds selected from a screening of 5,807 phytochemical compounds from 29 medicinal plants were CID_8299 and CID_71346280, with docking scores of -5.786 and -6.
View Article and Find Full Text PDFChemphyschem
December 2024
University of Ioannina, Chemistry, 45110, Ioannina, GREECE.
The solvation structure and dynamics of the thiocyanate anion at infinite dilution in mixed N, N-Dimethylformamide (DMF)-water liquid solvents was studied using classical molecular dynamics simulation techniques. The results obtained have indicated a preferential solvation of the thiocyanate anions by the water molecules, due to strong hydrogen bonding interactions between the anion and water molecules. A first hydration shell at short intermolecular distances is formed around the SCN- anion consisting mainly by water molecules, followed by a second shell consisting by both DMF and water molecules.
View Article and Find Full Text PDFChemMedChem
December 2024
Universite de Dijon, Institut de Chimie Moleculaire, ICMUB CNRS UMR6302, 9, avenue Alain Savary, 21078, Dijon, FRANCE.
Fluorescence detection of DNA and RNA G-quadruplexes (G4s) is a very efficient strategy to assess not only the existence and prevalence of cellular G4s but also their relevance as targets for therapeutic interventions. Among the fluorophores used to this end, turn-on probes are the most interesting since their fluorescence is triggered only upon interaction with their G4 targets, which ensures a high sensitivity and selectivity of detection. We reported on a series of twice-as-smart G4 probes, which are both smart G4 ligands (whose structure is reorganized upon interaction with G4s) and smart fluorescent probes (whose fluorescence is turned on upon interaction with G4s).
View Article and Find Full Text PDFJAMA Neurol
December 2024
Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, Korea.
Importance: The temporal dynamics of serum glial fibrillary acidic protein (sGFAP) and serum neurofilament light chain (sNfL) as biomarkers of disease activity for neuromyelitis optica spectrum disorder (NMOSD) remain underexplored.
Objective: To determine optimal timing for assessing sGFAP and sNfL, establish cutoff values differentiating between attacks and remissions in NMOSD, and evaluate these findings across independent cohorts.
Design, Setting, And Participants: This retrospective, longitudinal, multicenter cohort study was conducted among patients with aquaporin-4 antibody (AQP4-IgG)-positive NMOSD.
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