Revealing the interaction mechanism between bovine serum albumin (BSA) and a fluorescent coumarin derivative: A multispectroscopic and in silico approach.

The interaction of biomacromolecules with each other or with the ligands is essential for biological activity. In this context, the molecular recognition of bovine serum albumin (BSA) with 4-(Benzo[1,3]dioxol-5-yloxymethyl)-7-hydroxy-chromen-2-one (4BHC) is explored using multispectroscopic and computational techniques. UV-Vis spectroscopy helped in predicting the conformational variations in BSA. Using fluorescence spectroscopy, the quenching behaviour of the fluorophore upon interaction with the ligand is examined, which is found to be a static type of quenching; fluorescence lifetime studies further verify this. The binding constant is discovered to be in the range of 104 M-1, which indicates the moderate type of association that results in reversible binding, where the transport and release of ligands in the target tissue takes place. Fourier-transform infrared spectroscopy (FT-IR) measurements validate the secondary structure conformational changes of BSA after complexing with 4BHC. The thermodynamic factors obtained through temperature-dependent fluorescence studies suggest that the dominant kind of interaction force is hydrophobic in nature, and the interaction process is spontaneous. The alterations in the surrounding microenvironment of the binding site and conformational shifts in the structure of the protein are studied through 3D fluorescence and synchronous fluorescence studies. Molecular docking and molecular dynamics (MD) simulations agree with experimental results and explain the structural stability throughout the discussion. The outcomes might have possible applications in the field of pharmacodynamics and pharmacokinetics.

Phytoconstituents of Ashwagandha as potential inhibitors of human islet amyloid polypeptide (hIAPP): an in silico investigation.

Amylin or human islet amyloid polypeptide (hIAPP) is a small peptide co-secreted with insulin. Its peripheral aggregation on the lipid bilayer leads to fibril formation. The formation of hIAPP fibrils is hypothesized to rupture the membrane of ß -cells, which culminates in ß-cell death. Following additional studies, amylin fibril formation is a hallmark of T2DM and is also implicitly responsible for Alzheimer's disease. This study reports the virtual screening of 1000 phytoconstituents of traditional Indian medicinal plants to get potential inhibitors of amylin, which will likely restrict and block amyloid aggregation, preventing the progression of T2DM and Alzheimer's illness. The compounds having drug-likeness properties (acquired from ADMET calculations) and highest binding affinities (from molecular docking) are subjected to molecular dynamics (MD) simulation to investigate the temporal stability of the conformations of the complexes. This study discovers that Withaferin A and Withacoagulin have the highest binding affinity for amylin, and their stability with amylin was verified further by parameters such as RMSD, RMSF, number of H-bonds and MMPBSA. Individual principle component analysis (PCA) confirms the stable complex formation of amylin with Withaferin A and Withacoagulin. We strongly believe that wet-lab experiments and clinical trials will help to validate our computational findings.Communicated by Ramaswamy H. Sarma.