Understanding the Structural and Dynamic Effects of Protein Palmitoylation: A Computational Approach

Calnexin, a critical chaperone protein in the endoplasmic reticulum (ER), plays a vital role in glycoprotein folding and quality control. This study investigates how palmitoylation, a post-translational lipid modification, affects calnexin’s structural and functional dynamics. Using molecular dynamics (MD) simulations, we analysed the impact of palmitoylation at specific cysteine residues on the protein's stability and interactions. Both palmitoylated and non-palmitoylated forms of calnexin were examined to better understand its role in ER quality control and the glycoprotein folding process. Our findings revealed that palmitoylation induces conformational changes in calnexin, improving its stability and potentially altering its interactions with ER-associated proteins. These structural changes suggest that palmitoylation plays a significant role in modulating calnexin’s function, which may have broader implications for protein dynamics and cellular homeostasis. The results underscore the importance of lipid modifications in maintaining ER function and highlight potential links between calnexin palmitoylation and protein folding disorders.