作为二型糖尿病的潜在治疗药物，蛋白质酪氨酸磷酸酯酶1B（PTP1B）的抑制剂研究一直备受关注。而其中一种二齿类抑制剂由于其普遍较高的选择性和活性，又是抑制剂的研究重点和热点。本文采用分子动力学方法取样，MM/GBSA方法计算了1个二齿类PTP1B抑制剂与PTP1B及其2个同家族酶TCPTP和SHP-2的结合自由能，得到了与实验活性值相符的结果。同时基于MM/GBSA的能量分解计算表明，抑制剂与PTP1B第2位点附近的2个残基ARG24和ARG254有很强的相互作用，与其他2个酶第2位点的相互作用则有所减弱，尤其是SHP-2，几乎没有实质性相互作用。这应该是抑制剂产生选择性的关键。同时活性位点附近的残基PHE182也与抑制剂分子有很强的相互作用，相比TCPTP也有很大优势。希望这些信息在进一步提升PTP1B抑制剂的选择性和活性方面提供帮助。

As a kind of potential drug for treating the Type II diabetes, the inhibitor of protein tyrosine phosphatase 1B (PTP1B) is an important research field, in which a kind of bidentate inhibitors is the research focus. In this paper, molecular dynamics simulation and MM/GBSA method were employed to calculate the binding free energy of the protein-ligand complexes. The rank of the predicted free energies of the complexes is well consistent with the experiment data. The energy decomposition analysis based on the MM/GBSA also indicates the importance of second binding site, especially the residue ARG24 and ARG254 of PTP1B, in producing selectivity against SHP-2, but not so high selectivity against TCPTP. Also the inhibitor has important interaction with the residue of PHE182 of PTP1B, this is another reason that produces the selectivity against TCPTP. We expect that the information obtained in this work can help to develop potential PTP1B inhibitors with more promising specificity.