Insights on Aggregation of Hen Egg-White Lysozyme from Raman Spectroscopy and MD Simulations

Protein misfolding and aggregation play a significant role in several neurodegenerative diseases. In the present work, the spontaneous aggregation of hen egg-white lysozyme (HEWL) in an alkaline pH 12.2 at an ambient temperature was studied to obtain molecular insights. The time-dependent changes in spectral peaks indicated the formation of beta sheets and their effects on the backbone and amino acids during the aggregation process. Introducing iodoacetamide revealed the crucial role of intermolecular disulphide bonds amidst monomers in the aggregation process. These findings were corroborated by Molecular Dynamics (MD) simulations and protein-docking studies. MD simulations helped establish and visualize the unfolding of the proteins when exposed to an alkaline pH. Protein docking revealed a preferential dimer formation between the HEWL monomers at pH 12.2 compared with the neutral pH. The combination of Raman spectroscopy and MD simulations is a powerful tool to study protein aggregation mechanisms.

Automated summary

Protein misfolding and aggregation play a significant role in neurodegenerative diseases. This study investigated the spontaneous aggregation of hen egg-white lysozyme in an alkaline environment, revealing the formation of beta sheets and the importance of intermolecular disulphide bonds in the aggregation process. Molecular dynamics simulations and protein docking studies supported these findings, providing insights into the unfolding of proteins at alkaline pH and the preferential dimer formation at pH 12.2 compared to neutral pH.