Exploring the molecular mechanisms underlying insulin analogs is important for protein engineering to design innovative drug proteins. Insulin aspart (IAsp) and insulin degludec (IDeg) are representative examples of insulin analogs with distinct release profiles synthesized by targeted mutagenesis in protein engineering. Despite their importance in diabetes treatment, there remains a gap in our understanding of the molecular basis for their differential release mechanisms. In this study, ordinary molecular dynamics simulation and steered molecular dynamics are utilized to investigate the structural stability, solubility analysis, and monomer interactions of these insulins, with the aim to explain the mesoscale differences between the two insulin release mechanisms. Simulation findings have further been validated through experimental verification, shedding light on the intricate mechanisms underlying insulin release and providing valuable insights into pharmaceutical implications and potential advancements in the design of insulin therapy.

中文翻译：

---

为什么门冬胰岛素和德谷胰岛素表现出不同的释放机制


探索胰岛素类似物的分子机制对于蛋白质工程设计创新药物蛋白质非常重要。门冬胰岛素 (IAsp) 和德谷胰岛素 (IDeg) 是通过蛋白质工程中的定向诱变合成的具有不同释放曲线的胰岛素类似物的代表性例子。尽管它们在糖尿病治疗中很重要，但我们对其差异释放机制的分子基础的理解仍然存在差距。在本研究中，利用普通分子动力学模拟和引导分子动力学研究这些胰岛素的结构稳定性、溶解度分析和单体相互作用，旨在解释两种胰岛素释放机制之间的介观差异。模拟结果通过实验验证得到进一步验证，揭示了胰岛素释放背后的复杂机制，并为胰岛素治疗设计的药物影响和潜在进展提供了宝贵的见解。