促红细胞生成素(EPO)受体(EBP)激活剂的理论突变设计

Theoretical Mutation Design of Active Agent of Eryhropoietin and Its Receptor

采用分子动力学模拟的方法,构建了人促红细胞生成素模拟肽与其受体胞外结合片段的相互作用的分子动力学模型.通过对该模型的结构研究和理论分析,对模拟肽与受体结合机制提出了新的理论解释.根据EBP活性口袋的静电势分布,对二聚体小肽激活剂的每条链上的部分氨基酸进行了突变,分别用电性更强的氨基酸来代替部分疏水氨基酸,计算结果显示,突变后的二聚体小肽激活剂对EBP的"亲和力"明显增强.

Methods of molecular dynamics simulations were used to investigate the structure, dynamics and thermodynamics of the known complex between erythropoietin mimetic peptides（EMPs） and erythropoietin receptor（EpoR）. On the basis of these results, we designed new kinds of EMPs that has proposed significance in binding toreceptor. We used amino acid residues which have more electricity ability to replace the hydrophobic ones. According to our calculation results, the mutant type peptide has more binding ability to the EpoR. Our results illustrate a principle for fast identifying receptor-specific site important for receptor interralization, and for enhancing sensitivity to horm on and other agonist.