Structural analysis of

Background: Impaired meiosis can result in absence of sperm in the seminal fluid. This condition, namely non-obstructive azoospermia (NOA), is one of the reasons of male infertility. Despite the low number of studies on meiosis 1-associated protein ( Methods: We firstly performed an evolutionary conservation analysis for the variant positions. Afterwards, a comprehensive molecular modelling study was performed for the M1AP structure. By utilizing this model, protein dynamics were sampled for the wild-type and variants by performing molecular dynamics (MD) simulations. Results: All variant positions are highly conserved, indicating that they are potentially important for function. In MD simulations, none of the variants led to a general misfolding or loss of stability in the protein structure, but they did cause severe modifications in the conformational dynamics of M1AP, particularly through changes in local interactions affecting flexibility, hinge and secondary structure. Conclusions: Due to critical perturbations in protein dynamics, we propose that these variants may cause NOA by affecting important interactions regulating meiosis, particularly in wild-type M1AP deficiency since the variants are reported to be homozygous or bi-allelic in the infertile individuals. Our results provided reasonable insights about the M1AP structure and the effects of the variants to the structure and dynamics, which should be further investigated by experimental studies to validate.