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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.

By limiting chromosome erosion and end-to-end fusions, telomere integrity is critical for chromosome stability and cell survival. During mitotic cycles or due to environmental stresses, telomeres become progressively shorter and dysfunctional, thus triggering cellular senescence, genomic instability and cell death. To avoid such consequences, the telomerase action, as well as the Shelterin and CST complexes, assure the telomere's protection. Telomeric repeat binding factor 1 (TERF1), which is one of the primary components of the Shelterin complex, binds directly to the telomere and controls its length and function by regulating the telomerase activity. Several reports about TERF1 gene variations have been associated with different diseases, and some of them have linked these variations to male infertility. Hence, this paper can be advantageous to investigate the association between the missense variants of the TERF1 gene and the susceptibility to male infertility. The stepwise prediction of SNPs pathogenicity followed in this study was based on stability and conservation analysis, post-translational modification, secondary structure, functional interaction prediction, binding energy evaluation and finally molecular dynamic simulation. Prediction matching among the tools revealed that out of 18 SNPs, only four (rs1486407144, rs1259659354, rs1257022048 and rs1320180267) were predicted as the most damaging and highly deleterious SNPs affecting the TERF1 protein and its molecular dynamics when interacting with the TERB1 protein by influencing the function, structural stability, flexibility and compaction of the overall complex. Interestingly, these polymorphisms should be considered during genetic screening so they can be used effectively as genetic biomarkers for male infertility diagnosis.Communicated by Ramaswamy H. Sarma.