目的：观察羟基苯甲腈类抑制剂与Cdc25B磷酸酯酶相互作用的结合位点残基。方法利用分子动力学模拟的方法观察羟基苯甲腈类抑制剂A8H、3M8与Cdc25B磷酸酯酶之间的氢键作用和相互作用能，确定羟基苯甲腈类抑制剂与Cdc25B磷酸酯酶相互作用的结合位点残基。结果 A8H与Cdc25B结合位点残基Y382、D397、K399、R485、R488、R492形成氢键的概率分别为0、2．00％、0．40％、0．60％、0、0，而3M8与Cdc25B结合位点残基Y382、D397、K399、R485、R488、R492形成氢键的概率分别为11．38％、12．97％、0．80％、4．19％、94．41％、97．21％。D397、L398、C484、R485、R488、M505与A8H形成了较强相互作用（相互作用能数值分别为－2．40、－2．50、－2．30、－3．20、－4．00、－1．80 kcal／mol），Y382、D397、L398、C484、R485、R488、R492、M505与3M8形成了较强相互作用（相互作用能数值分别为－1．90、－5．30、－3．40、－1．00、－5．10、－19．40、－21．60、－1．50 kcal／mol）。结论羟基苯甲腈类抑制剂与Cdc25B磷酸酯酶的结合位点残基为Y382、D397、L398、C484、R485、R488、R492、M505。%Objective To investigate the binding site residues which are crucial for hydroxybenzonitrile inhibitors binding to Cdc25B phosphatase.Methods Molecular dynamics simulation was used to analyze the interactions of Cdc25B with hydroxybenzonitrile inhibitors A8H and 3M8.The hydrogen bond interaction analysis and interaction energy a-nalysis were then used to determine the residues which were crucial for hydroxybenzonitrile inhibitors binding.Results Hydrogen bond probabilities of A8H with Y382, D397, K399, R485, R488 and R492 were 0, 2.00%, 0.40%, 0.60%, 0 and 0, respectively.Hydrogen bond probabilities of 3M8 with Y382, D397, K399, R485, R488 and R492 were 11.38%, 12.97%, 0.80%, 4.19%, 94.41% and 97.21%, respectively.D397, L398, C484, R485, R488, M505 formed strong interactions with A8H ( interaction energies were -2.40 kcal/mol, -2.50 kcal/mol, -2.30 kcal/mol,-3.20 kcal/mol, -4.00 kcal/mol and -1.80 kcal/mol, respectively).Y382, D397, L398, C484, R485, R488, R492 and M505 formed strong interactions with 3M8 ( interaction energies were -1.90 kcal/mol, -5.30 kcal/mol,-3.40 kcal/mol, -1.00 kcal/mol, -5.10 kcal/mol, -19.40 kcal/mol, -21.60 kcal/mol and -1.50 kcal/mol, re-spectively).Conclusion Y382, D397, L398, C484, R485, R488, R492 and M505 are crucial for hydroxybenzonitrile inhibitors binding to Cdc25B phosphatase.
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