Intercellular communication between the cell plays an essential role in cell growth and cell formation, including migration, metabolism, and cell differentiation. Cell function and tissue homeostasis are maintained through gap junction intercellular communication (GJIC), thus regulating connexin hemichannels. Mis regulation of such connexin, especially connexin (Cx) 43, affects a comprehensive process, including cell differentiation, inflammation, and cell death. Mis regulation may be due to the missense variant in Cx43. Thus, we screened the complete set of mutations from public mutational databases and obtained 219 missense variants, which were then classified based on their pathogenicity, functional impact, stability, conservation, and physiochemical properties. Variant L214P was scrutinized to have the most deleterious, which was then modelled using the I-TASSER server and performed molecular docking analysis to screen potent inhibitors. The compound Kanamycin, Ginsenoside, and Astragaloside IV have better interactions with Cx43 mutant with a maximum of 5 hydrogen bonds. Ginsenoside is a compound that follows a Lipinski rule of five. Thus, the result obtained from this study suggests that Ginsenoside would be a better potent inhibitor for native and mutant Cx43.

中文翻译：

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连接蛋白 43 中最有害错义变异的比较计算方法及其有效抑制剂分析

细胞间的细胞间通讯在细胞生长和细胞形成中起着至关重要的作用，包括迁移、代谢和细胞分化。细胞功能和组织稳态通过间隙连接细胞间通讯 (GJIC) 维持，从而调节连接蛋白半通道。这种连接蛋白，尤其是连接蛋白 (Cx) 43 的错误调节会影响一个综合过程，包括细胞分化、炎症和细胞死亡。错误监管可能是由于 Cx43 中的错义变体。因此，我们从公共突变数据库中筛选出完整的突变集，获得了 219 个错义变异，然后根据它们的致病性、功能影响、稳定性、保守性和理化特性对其进行分类。变体 L214P 被仔细检查具有最有害的，然后使用 I-TASSER 服务器对其进行建模，并进行分子对接分析以筛选有效的抑制剂。化合物卡那霉素、人参皂苷和黄芪甲苷 IV 与最多 5 个氢键的 Cx43 突变体有更好的相互作用。人参皂苷是一种遵循李平斯基五定律的化合物。因此，从这项研究中获得的结果表明，人参皂苷是一种更有效的天然和突变 Cx43 抑制剂。