Zhang Ruojun, Akhtar Nahid, Wani Atif Khurshid, Raza Khalid, Kaushik Vikas
School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
School of Bioengineering and Biosciences, Lovely Professional University, Phagwara 144411, India.
Life (Basel). 2023 Jul 10;13(7):1532. doi: 10.3390/life13071532.
AKT1 is a serine/threonine kinase necessary for the mediation of apoptosis, angiogenesis, metabolism, and cell proliferation in both normal and cancerous cells. The mutations in the AKT1 gene have been associated with different types of cancer. Further, the AKT1 gene mutations are also reported to be associated with other diseases such as Proteus syndrome and Cowden syndromes. Hence, this study aims to identify the deleterious AKT1 missense SNPs and predict their effect on the function and structure of the AKT1 protein using various computational tools.
Extensive in silico approaches were applied to identify deleterious SNPs of the human AKT1 gene and assessment of their impact on the function and structure of the AKT1 protein. The association of these highly deleterious missense SNPs with different forms of cancers was also analyzed. The in silico approach can help in reducing the cost and time required to identify SNPs associated with diseases.
In this study, 12 highly deleterious SNPs were identified which could affect the structure and function of the AKT1 protein. Out of the 12, four SNPs-namely, G157R, G159V, G336D, and H265Y-were predicted to be located at highly conserved residues. G157R could affect the ligand binding to the AKT1 protein. Another highly deleterious SNP, R273Q, was predicted to be associated with liver cancer.
This study can be useful for pharmacogenomics, molecular diagnosis of diseases, and developing inhibitors of the AKT1 oncogene.
AKT1是一种丝氨酸/苏氨酸激酶，在正常细胞和癌细胞的凋亡、血管生成、代谢及细胞增殖介导过程中必不可少。AKT1基因突变与不同类型的癌症相关。此外，据报道AKT1基因突变还与其他疾病如变形综合征和考登综合征有关。因此，本研究旨在利用各种计算工具识别有害的AKT1错义单核苷酸多态性（SNP），并预测它们对AKT1蛋白功能和结构的影响。
应用广泛的计算机模拟方法来识别人类AKT1基因的有害SNP，并评估它们对AKT1蛋白功能和结构的影响。还分析了这些高度有害的错义SNP与不同形式癌症的关联。计算机模拟方法有助于降低识别与疾病相关SNP所需的成本和时间。
在本研究中，识别出12个可能影响AKT1蛋白结构和功能的高度有害SNP。在这12个SNP中，有4个SNP，即G157R、G159V、G336D和H265Y，预计位于高度保守的残基处。G157R可能影响配体与AKT1蛋白的结合。另一个高度有害的SNP，R273Q，预计与肝癌有关。
本研究可用于药物基因组学、疾病的分子诊断以及开发AKT1癌基因的抑制剂。
