采用分子模拟方法探究MIF与二芳基三唑类抑制剂的结合机理

Study on the binding mechanism of macrophage migration inhibitory factor with diaryltriazole by using molecular modeling approach

采用一整套分子模拟方法,从原子水平探究了MIF与二芳基三唑类抑制剂的微观结合模式及结构决定性因素。基于能量计算和结合机理的分析发现:高活性二芳基三唑类抑制剂的设计需要与N_(325)形成较强的氢键相互作用,与非极性氨基酸I_(64)形成较强的疏水相互作用,与Y_(36)、F_(113)、Y_(323)形成π-π相互作用。

In this paper,a set of integrated molecular modeling approach was used to explore the microscopic binding mode and structural determinants of MIF in complex with diaryltriazole inhibitors from the atomic level.Based on the analysis of energy calculation and binding mechanism,it is found that the design of highly potent diarytriazole inhibitors needs to form strong hydrogen bond interaction with N_(325),strong hydrophobic interaction with non-polar amino acid I_(64),and π-π interaction with Y_(36),F_(113) and Y_(323).