Institute for Computational Science and Technology , 6 Quarter, Linh Trung Ward, Thu Duc District, Ho Chi Minh City, Vietnam, and.
J Phys Chem B. 2012 Aug 30;116(34):10165-75. doi: 10.1021/jp302506a. Epub 2012 Aug 17.
Binding of curcumin, naproxen, and ibuprofen to Aβ1-40 peptide and its fibrils is studied by docking method and all-atom molecular dynamics simulations. The Gromos96 43a1 force field and simple point charge model of water have been used for molecular dynamics simulations. It is shown that if the receptor is a monomer then naproxen and ibuprofen are bound to the same place that is different from the binding position of curcumin. However all of three ligands have the same binding pocket in fibrillar structures. The binding mechanism is studied in detail showing that the van der Waals interaction between ligand and receptor dominates over the electrostatic interaction. The binding free energies obtained by the molecular mechanic-Poisson-Boltzmann surface area method indicate that curcumin displays higher binding affinity than nonsteroidal anti-inflammatory drugs. Our results are in good agreement with the experiments.
通过对接方法和全原子分子动力学模拟研究了姜黄素、萘普生和布洛芬与 Aβ1-40 肽及其原纤维的结合。使用了 Gromos96 43a1 力场和简单点电荷水模型进行分子动力学模拟。结果表明，如果受体是单体，则萘普生和布洛芬与姜黄素的结合位置不同。然而，所有三种配体在纤维状结构中都具有相同的结合口袋。详细研究了结合机制，表明配体与受体之间的范德华相互作用超过了静电相互作用。通过分子力学-泊松-玻尔兹曼表面积方法获得的结合自由能表明，姜黄素显示出比非甾体抗炎药更高的结合亲和力。我们的结果与实验结果吻合良好。
