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AKAP3 is needed for the formation of sperm flagellum structure, sperm motility, and male fertility. This study aims to model the AKAP3 tertiary structure and identify the probable impact of four mutations characterized in infertile men on the AKAP3 structure. The T464S, I500T, E525K, and I661T substitutions were analyzed using in silico methods. The secondary structure and three-dimensional model of AKAP3 were determined using PSI-BLAST based secondary structure prediction and Robetta servers. The TM-score was used to quantitatively measure the structural similarities between native and mutated models. All of the desired substitutions were classified as benign. I-Mutant results showed all of the substitutions decreased AKAP3 stability; however, the I500T and I661T were more effective. Superposition and secondary structure comparisons between native and mutants showed no dramatic deviations. Our study provided an appropriate model for AKAP3. Destabilization of AKAP3 caused by these substitutions did not appear to induce structural disturbances. As AKAP3 is involved in male infertility, providing more structural insights and the impact of mutations that cause protein functional diversity could elucidate the etiology of male fertility problems at molecular level.<\/jats:p>","DOI":"10.1038\/s41598-022-07513-9","type":"journal-article","created":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T11:06:11Z","timestamp":1646651171000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Structural modeling of human AKAP3 protein and in silico analysis of single nucleotide polymorphisms associated with sperm motility"],"prefix":"10.1038","volume":"12","author":[{"given":"Alemeh","family":"Rafaee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaheh","family":"Kashani-Amin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anahita Mohseni","family":"Meybodi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azadeh","family":"Ebrahim-Habibi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjan","family":"Sabbaghian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,7]]},"reference":[{"issue":"7","key":"7513_CR1","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1242\/jcs.00931","volume":"117","author":"M Luconi","year":"2004","unstructured":"Luconi, M. et al. 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