Faculty of Medicine, Erciyes University, Kayseri, Turkey.
Department of Medical Microbiology, Faculty of Medical Laboratory Sciences, University of Khartoum, Khartoum, Sudan.
BMC Genom Data. 2024 Jun 10;25(1):56. doi: 10.1186/s12863-024-01233-x.
Polymorphisms in IL1B play a significant role in depression, multiple inflammatory-associated disorders, and susceptibility to infection. Functional non-synonymous SNPs (nsSNPs) result in changes in the encoded amino acids, potentially leading to structural and functional alterations in the mutant proteins. So far, most genetic studies have concentrated on SNPs located in the IL1B promoter region, without addressing nsSNPs and their association with multifactorial diseases. Therefore, this study aimed to explore the impact of deleterious nsSNPs retrieved from the dbSNP database on the structure and functions of the IL1B protein.
Six web servers (SIFT, PolyPhen-2, PROVEAN, SNPs&GO, PHD-SNP, PANTHER) were used to analyze the impact of 222 missense SNPs on the function and structure of IL1B protein. Five novel nsSNPs (E100K, T240I, S53Y, D128Y, and F228S) were found to be deleterious and had a mutational impact on the structure and function of the IL1B protein. The I-mutant v2.0 and MUPro servers predicted that these mutations decreased the stability of the IL1B protein. Additionally, these five mutations were found to be conserved, underscoring their significance in protein structure and function. Three of them (T240I, D128Y, and F228S) were predicted to be cancer-causing nsSNPs. To analyze the behavior of the mutant structures under physiological conditions, we conducted a 50 ns molecular dynamics simulation using the WebGro online tool. Our findings indicate that the mutant values differ from those of the IL1B wild type in terms of RMSD, RMSF, Rg, SASA, and the number of hydrogen bonds.
This study provides valuable insights into nsSNPs located in the coding regions of IL1B, which lead to direct deleterious effects on the functional and structural aspects of the IL1B protein. Thus, these nsSNPs could be considered significant candidates in the pathogenesis of disorders caused by IL1B dysfunction, contributing to effective drug discovery and the development of precision medications. Thorough research and wet lab experiments are required to verify our findings. Moreover, bioinformatic tools were found valuable in the prediction of deleterious nsSNPs.
白细胞介素 1B（IL1B）中的多态性在抑郁症、多种炎症相关疾病和感染易感性中起着重要作用。功能非同义单核苷酸多态性（nsSNP）导致编码氨基酸的变化，可能导致突变蛋白的结构和功能改变。到目前为止，大多数遗传研究都集中在位于 IL1B 启动子区域的 SNP 上，而没有解决 nsSNP 及其与多因素疾病的关系。因此，本研究旨在探讨从 dbSNP 数据库中检索到的有害 nsSNP 对 IL1B 蛋白结构和功能的影响。
使用六个网络服务器（SIFT、PolyPhen-2、PROVEAN、SNPs&GO、PHD-SNP、PANTHER）分析了 222 个错义 SNP 对 IL1B 蛋白功能和结构的影响。发现五个新的 nsSNP（E100K、T240I、S53Y、D128Y 和 F228S）具有有害性，并对 IL1B 蛋白的结构和功能产生了突变影响。I-mutant v2.0 和 MUPro 服务器预测这些突变降低了 IL1B 蛋白的稳定性。此外，这些突变在蛋白质结构和功能中被发现是保守的，强调了它们的重要性。其中三个（T240I、D128Y 和 F228S）被预测为致癌的 nsSNP。为了分析突变结构在生理条件下的行为，我们使用 WebGro 在线工具进行了 50ns 的分子动力学模拟。我们的研究结果表明，突变值在 RMSD、RMSF、Rg、SASA 和氢键数量方面与 IL1B 野生型不同。
本研究提供了有关位于 IL1B 编码区的 nsSNP 的有价值的信息，这些 SNP 直接导致 IL1B 蛋白的功能和结构方面的有害影响。因此，这些 nsSNP 可以被认为是由 IL1B 功能障碍引起的疾病发病机制中的重要候选者，有助于有效的药物发现和精准医疗的发展。需要进行深入的研究和湿实验室实验来验证我们的发现。此外，生物信息学工具在有害 nsSNP 的预测中被发现很有价值。
