构效关系分析环氧水解酶对映体选择性机制OA

To investigate the effect mechanism of substrates substituent groups on the enantioselectivi-ty of epoxide hydrolases,the Three-Dimensional Quantitative Structure-Activity Relationship(3D-QSAR)model was constructed between epoxides and AuEH2 mutant enantioselectivity.Comparative Molecular Field Analysis(CoMFA)and Comparative Molecular Similarity Indices Analysis(CoM-SIA)models were constructed using the Partial Least Squares(PLS)method with the enantiomer ra-tios E as the dependent variables.The relevant statistical indicators of CoMFA and CoMSIA models met the standards.The CoMSIA model showed the hydrophobic and electrostatic field contribution factors were 45.5%and 30.0%.The E values of 17 training sets and 3 test sets predicted by CoMSIA model are highly consistent with the experimental values.Based on the above 3D-QSAR model,two high value-added epoxides 2-(2-fluorophenyl)oxirane(21a)and 2-[(3-methoxyphenoxy)methyl]ox-irane(22a)with high E values of 85 and 54,respectively,were predicted and verified by experiments.The constructed 3D-QSAR model was robust and effective for prediction.The hydrophobic and elec-trostatic fields of epoxides play the most important roles in determining the enantioselectivity of AuEH2 mutants.The 3D-QSAR model provides a theoretical basis for enantioselectivity recognition mechanism of epoxide hydrolases.