Effects of hesperidin, a flavanone glycoside interaction on the conformation, stability, and aggregation of lysozyme: multispectroscopic and molecular dynamic simulation studies?

Abstract

Hesperidin (HESP), a flavanone glycoside, shows high antioxidant properties and possess ability to go through the blood-brain barrier. Therefore, it could be a potential drug molecule against aggregation based diseases such as Alzheimer's, Parkinson's, and systemic amyloidoses. In this work, we investigated the potential of HESP to interact with hen egg-white lysozyme (HEWL) monomer and prevent its aggregation. The HESP-HEWL binding studies were performed using a fluorescence quenching technique, molecular docking and molecular dynamics simulations. We found a strong interaction of HESP with the lysozyme monomer (Ka, ~ 5 × 10(4) M(-1)) mainly through hydrogen bonding, water bridges, and hydrophobic interactions. We showed that HESP molecule spanned the highly aggregation prone region (amino acid residues 48-101) of HEWL and prevented its fibrillar aggregation. Further, we found that HESP binding completely inhibited amorphous aggregation of the protein induced by disulfide-reducing agent tries-(2-carboxyethyl) phosphine. Conformational and stability studies as followed by various tertiary and secondary structure probes revealed that HESP binding only marginally affected the lysozyme monomer conformation and increased both stability and reversibility of the protein against thermal denaturation. Future studies should investigate detail effects of HESP on solvent dynamics, structure, and toxicity of various aggregates. The answers to these questions will not only target the basic sciences, but also have application in biomedical and biotechnological sciences.

Spectroscopic investigation of the effects of aqueous‐phase prepared CdTe quantum dots on protein hemoglobin at the molecular level

“…Synchronous fluorescence spectroscopy here was used to provide characteristic information about the microenvironment in the vicinity of the chromospheres . In experiments, information about the tyrosine and tryptophan residues was obtained by fixing the wavelength intervals at 15 or 60 nm, respectively . The inner filter effect has been considered and the results showed have been corrected.…”

Multi‐spectroscopic and molecular dynamics simulations investigation of the binding mechanism of polybrominated diphenyl ethers to hen egg white lysozyme

“…The different mechanisms of fluorescence quenching is mainly dynamic quenching, static quenching, and non‐radiative energy transfer. Dynamic quenching and static quenching can be distinguished by their differing dependence on temperature . For dynamic quenching, higher temperatures lead to intensified energy transfer and a higher quenching constant.…”

Binding of hydroxylated polybrominated diphenyl ethers with human serum albumin: Spectroscopic characterization and molecular modeling

“…Fluorescence quenching proceeds via different mechanisms and is usually classified as dynamic quenching, static quenching, and non‐radiative energy transfer. With increase in temperature, the quenching rate constants increase and decrease in the dynamic and static quenching phenomena, respectively . If the Stern–Volmer quenching constant ( K sv ) is inversely correlated to temperature, then the quenching mechanism is predicted to be a static mechanism, as increase in the temperature probably decreases the complex stability .…”

“…In recent years, interactions among small molecules, drugs, and surfactants with proteins have been studied extensively, particularly the structural aspects, because it is important to elucidate the molecular aspects of binding to establish the structure–function relationship on the one hand and drug design and efficacy on the other hand . In particular, affinity, toxicity, and structural modifications of serum proteins have been studied to determine the efficacy of drug distribution in the target sites.…”