Bcr-Abl SH3与RIN1富含脯氨酸的序列结合,激活Bcr-Abl酪氨酸激酶活性,引起慢粒患者对伊马替尼耐药,为改变两者结合方式解决耐药问题,笔者对Bcr-Abl SH3结构域活性位点进行分析。Pep Site2.0软件分析RIN1与Bcr-Abl SH3结合部位及特点,选择突变位点,VMD1.8.7和NAMD2.6软件动态模拟获取稳定的SH3突变体结构,Pep Site2.0分析突变体和RIN1结合能力大小。两者结合部位位于SH3 90-118氨基酸位点,3种突变方式中双位点突变效果明显优于单位点及缩短的片段,单位点突变中并非所有被选择的位点突变后结合能力都提高,说明RIN1与SH3结合不仅依赖结合部位的特异氨基酸,其周围的氨基酸对维持两者的结合有着至关重要的作用。 Bcr-Abl SH3 binds to the proline-rich sequence of RIN1 and activates the Bcr-Abl tyrosine kinase activity, resulting in resistance to imatinib in CML patients. In order to change the combination of Bcr-Abl SH3 and drug resistance, Bcr-Abl SH3 domain active site analysis. Pep Site2.0 software analysis of RIN1 and Bcr-Abl SH3 binding sites and characteristics of the selected mutation sites, VMD1.8.7 and NAMD2.6 software dynamic simulation to obtain stable SH3 mutant structure, Pep Site2.0 analysis of the mutant and RIN1 binding Ability size. The binding sites were located at amino acid residues SH3 90-118. The double-site mutation effect of the three mutations was significantly better than that of the single site and the shortened fragment. Not all selected sites in the site-directed mutagenesis increased their binding ability after mutation , Indicating that binding of RIN1 to SH3 depends not only on the specific amino acids at the binding site but also around the amino acids that are crucial for maintaining their binding.