BACKGROUND AT1R (Angiotensin II type 1 receptor) is the main component of RAS (renin-angiotensin system) system, which activates when ANG II (angiotensin II) binds to it. AT1R helps in maintaining osmotic homeostasis and blood pressure regulation. A huge number of polymorphism are associated with AT1R and few of them were studied and found to be associated with the diseases and drug efficacy. Although it is a very important receptor most of the polymorphisms (SNPs) were not studied for their implications in diseases. A huge number of polymorphisms are reported in the databases for AT1R, which provide an avenue to explore these polymorphisms for their implications in protein structure, function and drug efficacy. METHODS In the current study, all the SNPs (10234) reported in NCBI were analyzed and SNPs that were important in protein structure and drug interactions were identified. Structures of these polymorphic forms were modeled and in silico drug interaction studies were carried out. RESULTS The result of the interaction studies with polymorphism was in correlation with the reported case. Two SNP mutated structures of AT1R i.e. rs780860717 (G288T), rs868647200 (A182C) show considerably less binding affinities in the case of all angiotensin receptor blockers (ARBs). As a result, these polymorphisms may show less efficacy toward these ARBs. The other mutated structures rs12721226 (A163G), rs749234826 (A292G), rs775810028 (A87G), show increased binding affinities in case of Eprosartan and most of the mutated structures shows increased binding affinity toward Telmisartan than the wild type AT1R. Similarly, these polymorphisms may show increased efficacy in the case of these two ARBs. CONCLUSION The outcome of the study will help in designing better drugs in the near future with broader spectrum. Furthermore, in vitro and in vivo studies can be designed according to the current results.

中文翻译：

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探索 AT1R 多态性对其功能、结构和药物相互作用的作用的计算机方法。

背景 AT1R（血管紧张素 II 1 型受体）是 RAS（肾素-血管紧张素系统）系统的主要成分，当 ANG II（血管紧张素 II）与其结合时激活。AT1R 有助于维持渗透压稳态和血压调节。大量的多态性与AT1R相关，其中很少有研究发现与疾病和药物疗效有关。尽管它是一种非常重要的受体，但大多数多态性 (SNP) 并未对其在疾病中的影响进行研究。AT1R 的数据库中报告了大量的多态性，这为探索这些多态性对蛋白质结构、功能和药物功效的影响提供了途径。方法 在目前的研究中，分析了 NCBI 中报告的所有 SNP (10234)，并确定了在蛋白质结构和药物相互作用中重要的 SNP。对这些多晶型的结构进行了建模，并进行了计算机药物相互作用研究。结果多态性交互作用研究结果与报告病例相关。AT1R 的两个 SNP 突变结构，即 rs780860717 (G288T)、rs868647200 (A182C) 在所有血管紧张素受体阻滞剂 (ARB) 的情况下显示出相当低的结合亲和力。因此，这些多态性可能对这些 ARB 显示出较低的功效。其他突变结构 rs12721226 (A163G), rs749234826 (A292G), rs775810028 (A87G), 在依普罗沙坦的情况下显示增加的结合亲和力，并且大多数突变结构显示对替米沙坦的结合亲和力比野生型AT1R增加。同样，在这两种 ARB 的情况下，这些多态性可能显示出更高的功效。结论 该研究的结果将有助于在不久的将来设计出更广谱更好的药物。此外，可以根据目前的结果设计体外和体内研究。