2型糖尿病(T2D)是由胰岛素抵抗(IR)和胰腺β细胞功能障碍引起的。AKT2蛋白是非常重要的蛋白信号通路,AKT2基因中的非同义SNP(nsSNP)可能与T2D相关。nsSNPs可以导致蛋白质稳定性的改变,酶活性,或结合特异性。这项研究的目的是研究nsSNP对AKT2蛋白结构和功能的影响,这可能导致IR和T2D的诱导。根据包括的一系列分析工具,该研究确定了20种被认为是最有害的变体(SIFT,Polyphen2,Mut-pred,SNAP2PANTHER,博士-SNP,SNP&Go,MUpro,Cosurf,和I-Mut)。两个突变,p.A179T和p.L183Q,根据PyMol确定的它们在蛋白质中的位置选择用于进一步研究。结果表明,突变,p.A179T和p.L183Q改变蛋白质的稳定性和功能特征,这可能会影响其功能。为了对这些影响进行更深入的分析,对野生型AKT2和两个突变体进行了分子动力学模拟(p。A179T和p.L183Q)。模拟评估了各种参数,包括温度,压力,密度,RMSD,RMSF,SASA,和区域,在100ps的时间内。根据仿真结果,与突变变体相比,野生型AKT2蛋白表现出更高的稳定性.发现突变p.A179T和p.L183Q引起蛋白质稳定性和功能性的降低。这些发现强调了nsSNP(突变p.A179T和p.L183Q)对AKT2的结构和功能的影响的重要性,这可能导致IR和T2D。然而,它们需要进一步验证未来的蛋白质功能,蛋白质-蛋白质相互作用,和大规模病例对照研究。验证后,这些结果将有助于识别和分层有IR和T2D风险的个体,以达到预防和治疗的目的.
Type 2 diabetes (T2D) develops from insulin resistance (IR) and the dysfunction of pancreatic beta cells. The AKT2 protein is very important for the protein signaling pathway, and the non-synonymous SNP (nsSNPs) in AKT2 gene may be associated with T2D. nsSNPs can result in alterations in protein stability, enzymatic activity, or binding specificity. The objective of this study was to investigate the effect of nsSNPs on the AKT2 protein structure and function that may result in the induction of IR and T2D. The study identified 20 variants that were considered to be the most deleterious based on a range of analytical tools included (SIFT, PolyPhen2, Mut-pred, SNAP2, PANTHER, PhD-SNP, SNP&Go, MUpro, Cosurf, and I-Mut). Two mutations, p.A179T and p.L183Q, were selected for further investigation based on their location within the protein as determined by PyMol. The results indicated that mutations, p.A179T and p.L183Q alter the protein stability and functional characteristics, which could potentially affect its function. In order to conduct a more in-depth analysis of these effects, a molecular dynamics simulation was performed for wildtype AKT2 and the two mutants (p.A179T and p.L183Q). The simulation evaluated various parameters, including temperature, pressure, density, RMSD, RMSF, SASA, and Region, over a period of 100 ps. According to the simulation results, the wildtype AKT2 protein demonstrated higher stability in comparison to the mutant variants. The mutations p.A179T and p.L183Q were found to cause a reduction in both protein stability and functionality. These findings underscore the significance of the effects of nsSNPs (mutations p.A179T and p.L183Q) on the structure and function of AKT2 that may lead to IR and T2D. Nevertheless, they require further verifications in future protein functional, protein-protein interaction, and large-scale case-control studies. When verified, these results will help in the identification and stratification of individuals who are at risk of IR and T2D for the purpose of prevention and treatment.