Homology Modelling, Molecular Docking and Molecular Dynamics Simulation Studies of CALMH1 against Secondary Metabolites of Bauhinia variegata to Treat Alzheimer's Disease.

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 Bauhinia variegata 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. Bauhinia variegata 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.

Screening and identification of secondary metabolites in the bark of Bauhinia variegata to treat Alzheimer's disease by using molecular docking and molecular dynamics simulations.

Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE) acts as a promising protein targets for which drug as an inhibitor can be designed to treat Alzheimer's Disease. Different flavonoids and alkaloids of Bauhinia variegata were used as an inhibitor to target the protein. The current in silico study was carried out to explore the binding patterns of flavanoids and alkaloids against Acetylcholinesterase (PDB ID: 4PQE) and Butyrylcholinesterase (PDB ID: 1P0I) using molecular docking and molecular dynamics simulations approach. Molecular docking result shows that Dihydroquercetin (CID:439533) binds with the active region of AChE and BChE. Using molsoft, molinspiration, and pkCSM all the properties of the candidate were analyzed. The best compound Dihydroquercetin was compared with Donepezil drug through molecular dynamic simulation studies. The analysis of Molecular Dynamics Simulations showed that AChE and AChE-Dihydroquercetin complex became stable at 3000 ps and there was little conformational change in BChE and BChE-Dihydroquercetin complex. The in silico study finally predicts that Dihydroquercetin may act as a good inhibitor for treating Alzheimer's disease and further in vitro and in vivo studies may prove its therapeutic potential.Communicated by Ramaswamy H. Sarma.

Preparation of Sliver and Selenium Nanoparticles and Its Characterization by Dynamic Light Scattering and Scanning Electron Microscopy.

AIM: In our study, two different methods were used to determine the size and size distribution of the sliver and selenium nanoparticles via dynamic light scattering (DLS) and scanning electron microscopy (SEM). BACKGROUND: Nanotechnology dealing with metal and metalloid nanoparticles has been usually applied in nearly each field of science, engineering, and technology including biology and medicine etc due to presence of size and shape dependent unusual physical and chemical properties. In the most recent decade, numerous groups including appreciably developed metal and metalloid nanoparticles based theranostic approaches for the treatment of almost human diseases. Amongst many nanoparticles, recently silver and selenium nanoparticles have been broadly used in the antimicrobial coatings, textiles, paints, keyboards, engineering, food industry, electronics, cosmetics, bio-sensing, wound dressings, and even in biomedical devices. METHODS: In our study, silver nanoparticles were prepared by using the chemical reduction method. Selenium nanoparticles (SeNPs) were synthesized by the chemical reduction of sodium selenite by glutathione (reduced form) and stabilized by bovine serum albumin (BSA). Characterization of silver and selenium nanoparticles samples were analyzed by dynamic light scattering (DLS) and Scanning Electron Microscopy (SEM). CONCLUSIONS: Due to characterization by DLS technique, nanoparticles size was found the range of 79.22 nm and 178 nm for Sliver and Selenium Nanoparticles respectively. Sliver nanoparticles shown morphological average size and shape with SEM reveals spherical shape particles with the size of 80.32 nm whereas Selenium nanoparticles shown rod shape particles with the size of 74.29 nm.