PTP1B和1,2-萘醌类抑制剂的分子动力学模拟  

MD Simulations of PTP1B-Inhibitor Complex

作　　者：潘咏梅[1] 侯廷军[2] 计明娟[1] 徐筱杰[2] 叶学其[1] 

机构地区：[1]中国科学院研究生院,北京100039 [2]北京大学化学与分子工程学院,北京100871

出　　处：《化学学报》2004年第2期148-152,共5页Acta Chimica Sinica

基　　金：国家自然科学基金 (Nos.2 0 2 730 83 ;2 9992 590 )资助项目

摘　　要：采用分子动力学和分子力学相结合的方法 ,研究了一类 1,2 萘醌类抑制剂与酪氨酸蛋白磷酸酯酶PTP1B之间的相互作用模式 .计算得到的抑制剂和靶酶之间的相互作用模式显示范德华相互作用、疏水相互作用以及氢键作用是主要的作用模式 .计算结果还表明抑制剂和PTP1B的相互作用能ΔE越低 ,抑制剂活性越高 .通过计算各种能量对ΔE的贡献 ,以及对复合物结构参数的分析 ,发现抑制剂和受体之间疏水相互作用是造成抑制剂活性差别的主要原因 .The interaction pattern between PTP1B (one kind of protein tyrosine phosphatase) and its inhibitors (1,2 naphthoquinone derivatives) was investigated by using molecular mechanics and molecular dynamics. From the calculations, it can be found that the van der Waals interactions, the hydrophobic interactions, as well as the H bonding interactions are crucial for ligand binding. Meanwhile, the calculated results show that the interaction energy, Δ E , is closely correlated with the activity of inhibitors. In addition, from the calculation of contribution of the van der Waals and electrostatic interactions to Δ E and the analyses of the predicted structures of the complex, we found that the difference of the activities of inhibitors is attributed to the hydrophobic interaction, which afford us important information for designing non acid PTP1B inhibitors.

关 键 词：1 2-萘醌类抑制剂 酪氨酸蛋白磷酸酯酶 PTPlB 分子动力学 相互作用 作用模式 糖尿病 

分 类 号：O643.1[理学—物理化学]