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

Abstract

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 Huperzia serrata 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.

Mechanistic Insight into the Binding of Huperzine a with Human Transferrin: Computational, Spectroscopic and Calorimetric Approaches

“…HupA showed excellent binding affinity to Tf with a binding constant of 0.2 × 10 6 M –1 and is comparable to the binding constant obtained for binding of HupA with HSA. 28 Hence, the in silico observations coupled with the fluorescence binding affirm significant binding of HupA to Tf.…”

“…Hup A has shown inhibitor effects against the tetrameric form of ACh, which is present in abundance, and other drugs such as rivastigmine inhibit the scarce monomeric form . A recent study reported binding of HupA with the most abundant plasma protein, human serum albumin (HSA) . Thus, in lieu of the importance of Tf in AD therapeutics and the potential of HupA as an excellent therapeutic candidate for AD, this study was performed to decipher the binding mechanism of HupA with Tf.…”

“… 27 A recent study reported binding of HupA with the most abundant plasma protein, human serum albumin (HSA). 28 Thus, in lieu of the importance of Tf in AD therapeutics and the potential of HupA as an excellent therapeutic candidate for AD, this study was performed to decipher the binding mechanism of HupA with Tf. In this study, we used molecular docking and molecular dynamic (MD) simulation approaches along with free energy landscape (FEL) and principal component analysis (PCA) to study the binding potential of HupA toward Tf.…”

Inhibition of Microtubule Affinity Regulating Kinase 4 by Metformin: Exploring the Neuroprotective Potential of Antidiabetic Drug through Spectroscopic and Computational Approaches

“…In a bid to maintain the structural conformation of the protein, hydrogen bonds play a pivotal role [ 18 ]. The analysis of hydrogen bonding aids in assessment of the stability of the protein and protein–ligand complexes [ 19 ]. Thus, herein, we analysed the intramolecular hydrogen bonding to decipher the stability of the MARK4 and MARK4–Mtf complex ( Figure 4 A).…”

Molecular Insight into the Binding of Astilbin with Human Serum Albumin and Its Effect on Antioxidant Characteristics of Astilbin

“…The two well-known binding sites available on HSA are Sudlow site I and II, located in subdomain IIA and IIIA [ 17 ]. A pivotal step in the domain of drug discovery is the investigation of the pharmacokinetics and pharmacodynamics of drugs [ 18 ]. The abundance of HSA makes it an important factor in the pharmacokinetic behavior of many drugs as it affects their efficacy and delivery rate, and the binding of a drug to HSA is a critical factor determining its pharmacological profiling and distribution [ 19 ].…”