hIL-6·hIL-6Rα·gp130三元复合物的结构预测

Structural Prediction on the Compound hIL-6·hIL-6Rα·gp130.

通过Delphi方法分析人白介素 6 (humaninterleukin 6 ,hIL 6 ) /人白介素 6受体α亚基 (humaninterleukin 6receptorαsubunit,hIL 6Rα)复合物、gp130 (βsubunit)的空间构象的表观静电分布 ,利用分子对接方法研究 gp130与hIL 6 /hIL 6Rα复合物作用形成三元复合物的空间构象 ,经过分子力学优化、分子动力学常温动态模拟借助分子间相互作用 (范德华力、氢键、盐键等 )、反应自由能理论探讨hIL 6·hIL 6Rα·gp130复合物稳定构象结合部位的结构域 .分析结果表明 ,gp130蛋白表面富集较强的负电势 ,复合物hIL 6 /hIL 6R一侧表面富集较强的正电势 ,gp130借助蛋白表面的静电作用结合hIL 6 /hIL 6R复合物 ,介导hIL 6信号 ;hIL 6中的helix C、loop BC、loop CD参与同 gp130中的loopEF、linker、loopA′B′、loopB′C′、loopD′E′作用 ,hIL 6R中的loopA′B′、β strandE′参与同gp130中的loopA′B′、β strandE′作用 .

According to the surface electronic potential distribution of the compound hIL 6/hIL 6R and gp130 was analyzed by the program Delphi, the space conformation of the tertiary compound hIL 6·hIL 6R·gp130 is studied with Docking method. The stable structure of the tertiary compound is obtained during the optimization with molecular mechanics and molecular dynamics at normal temperature. The binding domain of the stable compound was discussed by intermolecular force(including Van der Waals force, hydrogen bond, salt link, etc) and reaction free energy theory. The results showed that the surface of gp130 enriches negative charges whereas the compound hIL 6/hIL 6R positive charges, gp130 combines hIL 6/hIL 6R with surface electrostatic interaction for transduction signal, helix C, loopBC, loopCD in hIL 6 participate in the interaction with the regions loopEF,linker, loopA′B′, loopB′C′, loopD′E′in gp130, and the regions loopA′B′, β strand E′ in hIL 6R are interacted with the regions loopA′B′, β strand E′ in gp130.