Jung Sung Hun, Kim Chang-Kyu, Lee Gunhee, Yoon Jonghwan, Lee Minho
Department of Biological Science, Sangji University, Wonju 26339, Korea.
Theragen Etex Bio Institute, Suwon 16229, Korea.
Genomics Inform. 2017 Dec;15(4):142-146. doi: 10.5808/GI.2017.15.4.142. Epub 2017 Dec 29.
More effective production of human insulin is important, because insulin is the main medication that is used to treat multiple types of diabetes and because many people are suffering from diabetes. The current system of insulin production is based on recombinant DNA technology, and the expression vector is composed of a preproinsulin sequence that is a fused form of an artificial leader peptide and the native proinsulin. It has been reported that the sequence of the leader peptide affects the production of insulin. To analyze how the leader peptide affects the maturation of insulin structurally, we adapted several simulations using 13 artificial proinsulin sequences. Three-dimensional structures of models were predicted and compared. Although their sequences had few differences, the predicted structures were somewhat different. The structures were refined by molecular dynamics simulation, and the energy of each model was estimated. Then, protein-protein docking between the models and trypsin was carried out to compare how efficiently the protease could access the cleavage sites of the proinsulin models. The results showed some concordance with experimental results that have been reported; so, we expect our analysis will be used to predict the optimized sequence of artificial proinsulin for more effective production.
更有效地生产人胰岛素很重要，因为胰岛素是用于治疗多种类型糖尿病的主要药物，且有许多人患有糖尿病。当前的胰岛素生产系统基于重组DNA技术，表达载体由前胰岛素原序列组成，该序列是人工前导肽与天然胰岛素原的融合形式。据报道，前导肽的序列会影响胰岛素的生产。为了从结构上分析前导肽如何影响胰岛素的成熟，我们使用13种人工胰岛素原序列进行了多次模拟。预测并比较了模型的三维结构。尽管它们的序列差异很小，但预测的结构有所不同。通过分子动力学模拟对结构进行了优化，并估计了每个模型的能量。然后，在模型与胰蛋白酶之间进行蛋白质-蛋白质对接，以比较蛋白酶能够多高效地接近胰岛素原模型的切割位点。结果与已报道的实验结果有一定的一致性；因此，我们期望我们的分析将用于预测人工胰岛素原的优化序列以实现更有效的生产。
