Mechanistic Insight into Binding of Huperzine A with Human Serum Albumin: Computational and Spectroscopic Approaches

• Published in: Molecules (Basel, Switzerland) Switzerland), 2022-01, Vol.27 (3), p.797
• Main Authors: Shamsi, Anas, Shahwan, Moyad, Khan, Mohd Shahnawaz, Alhumaydhi, Fahad A, Alsagaby, Suliman A, Al Abdulmonem, Waleed, Abdullaev, Bekhzod, Yadav, Dharmendra Kumar
• Format: Article
• Language: English
• Subjects: Albumin; Alkaloids - metabolism; Alzheimer's disease; Apoptosis; Binding; Binding sites; Circulatory system; Clinical trials; Computational neuroscience; Dementia; Drugs; drug–protein interactions; Fluorescence; fluorescence spectroscopy; Human serum albumin; Humans; Huperzine A; Hydrogen Bonding; Hydrogen bonds; Ligands; Molecular docking; Molecular Docking Simulation; Molecular dynamics; Molecular Dynamics Simulation; Neurodegeneration; neurodegenerative disorders; Neuroprotective Agents - metabolism; Oxidative stress; Pharmaceutical industry; Pharmacodynamics; Pharmacokinetics; Plasma; Polypeptides; Principal Component Analysis; Principal components analysis; Protein Binding; Proteins; Serum albumin; Serum Albumin, Human - metabolism; Sesquiterpenes - metabolism; Simulation; Spectrometry, Fluorescence - methods
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules27030797

Human serum albumin (HSA) is the most abundant protein in plasma synthesized by the liver and the main modulator of fluid distribution between body compartments. It has an amazing capacity to bind with multiple ligands, offering a store and transporter for various endogenous and exogenous compounds. Huperzine A (HpzA) is a natural sesquiterpene alkaloid found in and used in various neurological conditions, including Alzheimer's disease (AD). This study elucidated the binding of HpzA with HSA using advanced computational approaches such as molecular docking and molecular dynamic (MD) simulation followed by fluorescence-based binding assays. The molecular docking result showed plausible interaction between HpzA and HSA. The MD simulation and principal component analysis (PCA) results supported the stable interactions of the protein-ligand complex. The fluorescence assay further validated the in silico study, revealing significant binding affinity between HpzA and HSA. This study advocated that HpzA acts as a latent HSA binding partner, which may be investigated further in AD therapy in experimental settings.