The human zona pellucida (ZP) is an extracellular glycoprotein matrix surrounding the oocyte, playing a critical role in oocyte maturation, sperm-egg interactions during fertilization, and early embryonic protection. It comprises four glycoproteins, including ZP۱, which contributes to its structural integrity and function. Mutations in
ZP۱ have been linked to structural and functional abnormalities of the zona pellucida, leading to
female infertility associated with zona pellucida deficiency and Empty Follicle Syndrome (EFS). Among these, the
R۴۱۰W point mutation is associated with oocyte degeneration and the absence of a surrounding zona pellucida, underscoring its potential impact on protein stability and interaction dynamics. This study evaluates the effects of the
R۴۱۰W substitution on
ZP۱ protein stability and non-covalent interactions using bioinformatics tools. The sequence of the
ZP۱ protein was accessed from the uniprot database (P۶۰۸۵۲). The impact of the
R۴۱۰W variant on the stability of the
ZP۱ protein was assessed using MUpro, I-Mutant, and PremPS prediction tools. The findings from these tools were expressed as ΔΔG values, where a negative value indicates a destabilizing effect from a single point mutation, while a positive value in PremPS indicates a destabilizing mutation. Additionally, the PremPS tool was employed to calculate and visualize the non-covalent interactions involving residue ۴۱۰ with other residues in both the native and mutant forms of the
ZP۱ protein. The ΔΔG values obtained from the three online tools uniformly indicate a reduction in the stability of the mutant protein, with values of -۰.۶۸۷۹۷۴۲۳ for MUpro, -۰.۵۰ for I-Mutant ۲, and ۰.۷۱ for PremPS. Furthermore, the results from the PremPS database highlighted the loss of a hydrophobic bond between W۴۱۰ and P۵۳۷ residues, as well as some van der Waals interactions with Y۴۲۰ residue and two ionic bonds with E۴۳۹ residue that were present in the wildtype protein. Additionally, the mutant
ZP۱ protein exhibited one polar and one hydrophobic bond with E۴۰۸ that were not present in the wildtype. These findings highlight the potential implications of the
R۴۱۰W substitution on the structural integrity and stability properties of the
ZP۱ protein
