Structural insights into conformational stability of both wild-type and mutant Insulin Receptor Gene

Type 2 diabetes (T2D) poses a health challenge. It can lead to complications such as heart disease, hypertension, heart failure, and stroke. Factors like obesity and lack of activity can contribute to insulin resistance. The insulin receptor gene (INSR) is responsible for producing insulin receptors. When this gene malfunctions, it can contribute to the development of T2D. In this study, we investigated the stability of the structure of variants of INSR using an extended molecular dynamics simulation and the perturbation effect of compound CheBI_88339 on the protein structure. During the analysis, we observed that all three systems—the wild-type INSR, the R1191Q variant, and the R1191Q variant bound to compound CheBI_88339 (R1191Q-D) reached equilibrium in 30ns without any instability. Throughout the simulation process, it was generally observed that the wild-type INSR exhibited higher stability than the R1191Q variant and R1191Q-D. The root mean square deviation (RMSD) and root mean square fluctuation (RMSF) of INSR, R1191Q and the variant bound to compound CheBI_88339 (R1191Q-D) are 9.28Å, 10.35Å, 8.65Å, 2.59Å, 2.98Å, and 2.89Å respectively. These values indicate that the mutated INSR introduced levels of deviations and flexibility in the protein structure. However, considering the variant bound to compound CheBI_88339 suggests that this drug may contribute to stabilizing the dynamics of the mutant protein. Overall, our findings shed light on the effect of genetic variants and their impact on protein stability. This research provides further insight into the dynamics of INSR and the potential of CheBI_88339 in targeting INSR. However, this study is computational, and further experimental studies are required.