首页> 外文期刊>Journal of King Saud University >In silico prediction of deleterious single nucleotide polymorphism in human AKR1C3 gene and identification of potent inhibitors using molecular docking approach
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In silico prediction of deleterious single nucleotide polymorphism in human AKR1C3 gene and identification of potent inhibitors using molecular docking approach

机译:在硅中的斜体>斜体>利用分子对接方法鉴定有毒单核苷酸多态性的预测

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ObjectiveThe Aldo-keto reductase family consists of a number of enzymes which are essential to the catalysis of redox transformation and which are also involved in intermediate metabolism and detoxification. Several studies have been reported that the catalytic-dependent function of AKR1C family members isoforms and their essential roles in various cancer types including prostate cancer and play a key role in drug resistance and drug detoxification. The aim of the current study was to predict and analyze the deleterious single nucleotide polymorphism (SNP) that is highly associated with prostate cancer. In addition, to find the potent bioactive compounds as effective inhibitors against prostate cancer.MethodsVarious computational methods are employed to analyze the various non-synonymous single nucleotide polymorphisms (nsSNPs) in the AKR1C3 gene.ResultsA total of 18,594 SNPs data set of deleterious and non-coding synonymous were retrieved from the dbSNP database followed by various computational SNP prediction tools were performed to find the most deleterious nsSNP. A total of eight high-risk nsSNPs were predicted and most of the residue is present in the structural and functional conserved domain, hence, both wild type and mutant forms of AKR1C3 were selected for structural analysis. Besides, molecular docking, ADME, and Prime MM/GBSA calculations were also performed with plant derived bioactive compounds with AKR1C3 receptors. The results of the study depicted that the rs62621365 and its possible mutation A258C was considered as the most deleterious nsSNP and plant compounds such as Ginkgetin and Withaferin A shows best binding affinity with both wild type and mutant from of AKR1C3.ConclusionThe overall results depicted that nsSNPs may be considered for risk assessment against prostate cancer and for cure, the suggested plant derived bioactive compounds may act as potent inhibitors.
机译:客观的Aldo-keto还原酶系列由许多酶组成,这些酶对于氧化还原转化的催化是必不可少的,并且还参与中间代谢和排毒。据报道,若干研究表明,AKR1C家族成员同种型的催化作用及其在各种癌症类型中的基本作用,包括前列腺癌,并在耐药性和药物排毒中发挥关键作用。目前研究的目的是预测和分析与前列腺癌高度相关的有害单核苷酸多态性(SNP)。此外,为了发现有效的生物活性化合物作为针对前列腺癌的有效抑制剂。采用石英的计算方法来分析AKR1C3基因中的各种非同义单核苷酸多态性(NSSNPS)。培养和非 - 从DBSNP数据库中检索的代码数据库,后跟各种计算SNP预测工具,以查找最有疏忽的NSSNP。预测了总共八个高风险的NSSNP,并且在结构和功能保守域中存在大部分残留物,因此选择AKR1C3的野生型和突变形式进行结构分析。此外,还使用植物衍生的生物活性化合物与AKR1C3受体进行的分子对接,ADME和蛋白/ GBSA计算。研究结果表明,RS62621365及其可能的突变A258C被认为是最有害的NSSNP和植物化合物,如Ginkgetin和uperaferin A与AKR1C3的野生型和突变体显示出最佳结合亲和力。结论,结论NSSNP所描绘的整体结果可以考虑对前列腺癌和治愈的风险评估,建议的植物衍生的生物活性化合物可以充当有效的抑制剂。

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