VEGFR-2 与抑制剂Sunitinib 的分子对接及分子动力学研究

用分子对接方法研究了VEGFR-2 和抑制剂Sunitinib 的相互作用模式, 并对其复合物进行了10 ns 的分子动力学(Molecular Dynamics, MD)模拟. 结果表明, 抑制剂Sunitinib 能与VEGFR-2 中位于活性空腔的Glu885, Ile888, His1026,Asp1028, Asp1046 五个氨基酸残基形成疏水作用; 另外, VEGFR-2 中His1026, Cys1024, Asp1046 三个氨基酸残基能与Sunitinib 形成三个作用强度不同的氢键. 这些基团之间的相互作用是Sunitinib 抑制VEGFR-2 活性的关键因素. 研究结果可为VEGFR-2 抑制剂的结构改良、分子设计、合成提供理论参考, 并有助于寻找活性更高、效果更好的抗肿瘤药物.

Study on Docking and Molecular Dynamics Simulation between VEGFR-2 and the Inhibitor Sunitinib

Molecular docking were used to investigate the interaction of Sunitinib with VEGFR-2.A 10 ns molecular dynamics(MD) calculation was performed to study the complex and the results indicate that Sunitinib can produce hydrophobic interactions with the nonpolar side chains of the residues(Glu885,Ile888,His1026,Asp1028,Asp1046) in the binding pocket.Moreover,the three residues(His1026,Cys1024,Asp1046) ground Sunitinib can form H-bonds with Sunitinib,which can produce significant contribution to biological activities.The result of our simulation will provide theoretical basis for molecular structure improvement,molecular design,molecular synthesis of VEGFR-2 inhibitor,and will be useful in finding higher activity,better anticancer drugs.