Computational study of the potential impact of AURKC missense SNPs on AURKC-INCENP interaction and their correlation to macrozoospermia

Abstract

Aurora Kinase C (AURKC) is considered an important element in Chromosome Passenger Complex (CPC), its interaction with Inner Centromere Protein (INCENP) plays a critical role in the establishment and the recruitment of a stable CPC during spermatogenesis. Genetic variations of AURKC gene are susceptible to impact AURKC-INCENP interaction, which may affect CPC stability and predispose male subjects to macrozoospermia. In this study, we systematically applied computational approaches using different bioinformatic tools to predict the effect of missense SNPs reported on AURKC gene, we selected the deleterious ones and we introduced their corresponding amino acid substitutions on AURKC protein structure. Then we did a protein-protein docking between AURKC variants and INCENP followed by a structural assessment of each resulting complex using PRODIGY server, Yassara view, Ligplot + and we choose the complexes of the most impactful variants for molecular dynamics (MD) simulation study. Seventeen missense SNPs of AURKC were identified as deleterious between all reported ones. All of them were located on relatively conserved positions on AURKC protein according to Consurf server. Only the four missense SNPs; E91K, D166V, D221Y and G235V were ranked as the most impactful ones and were chosen for MD simulation. D221Y and G235V were responsible for the most remarkable changes on AURKC-INCENP structural stability, therefore, they were selected as the most deleterious ones. Experimental studies are recommended to test the actual effect of these two variants and their actual impact on the morphology of sperm cells.

Communicated by Ramaswamy H. Sarma

Keywords:

• Male infertility
• macrozoospermia
• AURKC gene
• molecular docking
• molecular dynamics simulation

Acknowledgements

The molecular dynamics simulation was conducted on the High-Performance Computing cluster of the National Center for Scientific and Technical Research (CNRST), Rabat, Morocco.

Disclosure statement

No potential conflict of interest was reported by the authors.

Funding

The author(s) reported there is no funding associated with the work featured in this article.

Authors’ contribution

SR, HC and HR conceived the idea and designed the objectives. SR performed the computational study. HH, AM, and AB participated in the data analysis. SR wrote the paper.

Data availability statement

The authors declare that all the data supporting the findings of this study are available within the paper.