Background: Wilson’s disease is a rare autosomal recessive genetic disorder of copper metabolism, which is characterized by hepatic and neurological disease. ATP7B encodes a transmembrane protein ATPase (ATP7B), which functions as a copper-dependent P-type ATPase. The mutations in the gene ATP7B (on chromosome 13) lead to Wilson’s disease and is highly expressed in the liver, kidney, and placenta. Consequently, this enzyme was considered a special topic in clinical and biotechnological research. For in silico analysis, the 3D molecular modeling of this enzyme was conducted in the I-TASSER web server.

Methods: For a better evaluation, the important characteristics of this enzyme such as the rare codons of the ATP7B gene were evaluated by online software, including a rare codon calculator (RCC), ATGme, LaTcOm, and Sherlocc program. Additionally, the multiple sequence alignment of this enzyme was studied. Finally, for evaluation of the effects of rare codons, the 3D structure of ATP7B was modeled in the Swiss Model and I-TASSER web server.

Results: The results showed that the ATP7B gene has 35 single rare codons for Arg. Additionally, RCC detected two rare codons for Leu, 13 single rare codons for Ile and 28 rare codons for the Pro. ATP7B gene analysis in minmax and sliding_window algorithm resulted in the identification of 16 and 17 rare codon clusters, respectively, indicating the different features of these algorithms in the detection of RCCs. Analyzing the 3D model of ATP7B protein showed that Arg816 residue constitutes hydrogen bonds with Glu810 and Glu816. Mutation of this residue to Ser816 cause these hydrogen bonds not to be formed and may interfere in the proper folding of ATP7B protein. Furthermore, the side chain of Arg1228 does not form any bond with other residues. By mutation of Arg1228 to Thr1228, a new hydrogen bond is formed with the side chain of Arg1228. The addition and deletion of hydrogen bonds alter the proper folding of ATP7B protein and interfere with the proper function of the ATP7B position. On the other hand, His1069 forms the hydrogen bonds with the His880 and this hydrogen bond adhere two regions of the protein together, which is critical in the final structural folding of ATP7B protein.

Conclusion: Previous studies show that synonymous and silent mutations have been linked to numerous diseases. Given the importance of synonymous and silent mutations in diseases, the aim of this study was to investigate the rare codons (synonymous codons) in the structure of ATP7B enzyme. By these analyses, a new understanding was developed and our findings can further be used in some fields of the clinical and industrial biotechnology.

背景：威尔逊氏病是一种罕见的铜代谢常染色体隐性遗传疾病，其特征是肝和神经系统疾病。ATP7B编码跨膜蛋白ATPase（ATP7B），其功能是依赖铜的P型ATPase。ATP7B基因（13号染色体上）的突变导致威尔逊氏病，并在肝，肾和胎盘中高度表达。因此，该酶被认为是临床和生物技术研究中的一个特殊主题。对于计算机分析，该酶的3D分子建模是在I-TASSER Web服务器中进行的。

方法：为了更好的评估，通过在线软件评估了该酶的重要特性，例如ATP7B基因的稀有密码子，包括稀有密码子计算器（RCC），ATGme，LaTcOm和Sherlocc程序。另外，研究了该酶的多序列比对。最后，为了评估稀有密码子的作用，在Swiss Model和I-TASSER Web服务器中对ATP7B的3D结构进行了建模。

结果：结果表明，ATP7B基因具有35个Arg的单个稀有密码子。此外，RCC为Leu检测到两个稀有密码子，为Ile检测到13个单个稀有密码子，为Pro检测到28个稀有密码子。用minmax和滑动窗口算法对ATP7B基因进行分析，分别鉴定出16个和17个稀有密码子簇，表明了这些算法在RCC检测中的不同特征。分析ATP7B蛋白的3D模型表明，Arg816残基与Glu810和Glu816构成氢键。此残基突变为Ser816会导致这些氢键无法形成，并可能干扰ATP7B蛋白的正确折叠。此外，Arg1228的侧链不与其他残基形成任何键。通过将Arg1228突变为Thr1228，在Arg1228的侧链上形成了一个新的氢键。氢键的添加和删除会改变ATP7B蛋白的正确折叠，并干扰ATP7B位置的正确功能。另一方面，His1069与His880形成氢键，该氢键将蛋白质的两个区域粘合在一起，这对于ATP7B蛋白质的最终结构折叠至关重要。

结论：先前的研究表明同义词和沉默突变与多种疾病有关。考虑到同义和沉默突变在疾病中的重要性，本研究的目的是研究ATP7B酶结构中的稀有密码子（同义密码子）。通过这些分析，形成了新的理解，我们的发现可进一步用于临床和工业生物技术的某些领域。