Centre de Biophysique Moléculaire, UPR 4301-Affiliated to the University of Orléans, CNRS, Orléans, France.
FEBS Lett. 2011 Aug 19;585(16):2599-603. doi: 10.1016/j.febslet.2011.07.014. Epub 2011 Jul 26.
To address the question of ligand entry process, we report targeted molecular dynamics simulations of the entry of the flexible ionic ligand GW0072 in the ligand binding domain of the nuclear receptor PPARγ. Starting with the ligand outside the receptor the simulations led to a ligand docked inside the binding pocket resulting in a structure very close to the holo-form of the complex. The results showed that entry process is guided by hydrophobic interactions and that entry pathways are very similar to exit pathways. We suggest that TMD method may help in discriminating between ligands generated by in silico docking.
为了解决配体进入过程的问题，我们报告了靶向分子动力学模拟，研究了柔性离子配体 GW0072 进入核受体 PPARγ 的配体结合域的过程。从配体在受体外部开始，模拟导致配体在结合口袋内对接，从而产生非常接近复合物的全构象的结构。结果表明，进入过程受疏水性相互作用的指导，进入途径与退出途径非常相似。我们建议 TMD 方法可帮助区分计算机对接产生的配体。
