CAJ | 학술논문

利用复合物指纹的虚拟筛选预测自分泌运动因子(ATX)抑制剂的结合位点,并通过与24个抑制剂(10个脂质和脂基抑制剂,14个小分子抑制剂)分子对接和动力学模拟表明, Thr209,Asp172,Tyr306,Phe210,Leu243,Leu213和Phe274是抑制剂结合位点的重要残基,且这些残基均通过侧链与抑制剂作用.利用3D-partner预测出与 ATX结合的蛋白为纤溶酶原激活物抑制剂1(rPAI-1),并通过同源模拟,得到rPAI-1的分子结构.利用软件 GRAMM将ATX与rPAI-1分子结构相结合,并通过分子动力学模拟确定与大分子抑制剂 rPAI-1作用的ATX重要残基Glu155和Ala158.
이용복합물지문적허의사선예측자분비운동인자(ATX)억제제적결합위점,병통과여24개억제제(10개지질화지기억제제,14개소분자억제제)분자대접화동역학모의표명, Thr209,Asp172,Tyr306,Phe210,Leu243,Leu213화Phe274시억제제결합위점적중요잔기,차저사잔기균통과측련여억제제작용.이용3D-partner예측출여 ATX결합적단백위섬용매원격활물억제제1(rPAI-1),병통과동원모의,득도rPAI-1적분자결구.이용연건 GRAMM장ATX여rPAI-1분자결구상결합,병통과분자동역학모의학정여대분자억제제 rPAI-1작용적ATX중요잔기Glu155화Ala158.
The composite fingerprint virtual screening was used to predicate the binding mode of autotoxin’s (ATX)inhibitor.Our results indicate that Thr209,Asp172,Tyr306,Phe210,Leu243, Leu213,and Phe274 are important residues for binding 24 inhibitors (10 lipid and lipid-based inhibitors and 14 small molecule inhibitors).We also predicted the binding mode of plasminogen activator inhibitor 1 (rPAI-1 )to ATX.Under the guidance of GRAMM software,the homology modeling of macromolecule inhibitor rPAI-1 showed it was docked to ATX.Through molecular dynamics simulation,we predicted the important residues Glu1 5 5 and Ala1 5 8 involved in the binding of macromolecule inhibitor rPAI-1 .