Bao J, Zhang D W, Zhang J Z H, Huang P Lee, Huang P Lin, Lee-Huang S
Department of Chemistry, New York University, New York, NY 10003, USA.
FEBS Lett. 2007 Jun 12;581(14):2737-42. doi: 10.1016/j.febslet.2007.05.029. Epub 2007 May 21.
Recent experimental study found that OLE (olive leaf extract) has anti-HIV activity by blocking the HIV virus entry to host cells [Lee-Huang, S., Zhang, L., Huang, P.L., Chang, Y. and Huang, P.L. (2003) Anti-HIV activity of olive leaf extract (OLE) and modulation of host cell gene expression by HIV-1 infection and OLE treatment. Biochem. Biophys. Res. Commun. 307, 1029; Lee-Huang, S., Huang, P.L., Zhang, D., Lee, J.W., Bao, J., Sun, Y., Chang, Y.-Tae, Zhang, J.Z.H. and Huang, P.L. (2007) Discovery of small-molecule HIV-1 fusion and integrase inhibitors oleuropein and hydroxytyrosol. Biochem. Biophys. Res. Commun. 354, 872-878, 879-884]. As part of a joint experimental and theoretical effort, we report here computational study to help identify and characterize the binding complexes of several main compounds of OLE (olive leaf extract) to HIV-1 envelop protein gp41. A number of possible binding modes are found by docking oleuropein and its metabolites, aglycone, elenolic acid and hydroxytyrosol, onto the hydrophobic pocket on gp41. Detailed OLE-gp41 binding interactions and free energies of binding are obtained through molecular dynamics simulation and MM-PBSA calculation. Specific molecular interactions in our predicted OLE/gp41 complexes are identified and hydroxytyrosol is identified to be the main moiety for binding to gp41. This computational study complements the corresponding experimental investigation and helps establish a good starting point for further refinement of OLE-based gp41 inhibitors.
最近的实验研究发现，橄榄叶提取物（OLE）通过阻断HIV病毒进入宿主细胞而具有抗HIV活性[李-黄，S.，张，L.，黄，P.L.，张，Y.和黄，P.L.（2003年）橄榄叶提取物（OLE）的抗HIV活性以及HIV-1感染和OLE处理对宿主细胞基因表达的调节。生物化学与生物物理研究通讯307，1029；李-黄，S.，黄，P.L.，张，D.，李，J.W.，鲍，J.，孙，Y.，张，Y.-泰，张，J.Z.H.和黄，P.L.（2００７年）小分子HIV-1融合和整合酶抑制剂橄榄苦苷和羟基酪醇的发现。生物化学与生物物理研究通讯354，872 - 878，879 - 884]。作为联合实验和理论研究工作的一部分，我们在此报告计算研究，以帮助识别和表征橄榄叶提取物（OLE）的几种主要化合物与HIV-1包膜蛋白gp41的结合复合物。通过将橄榄苦苷及其代谢产物、苷元、elenolic酸和羟基酪醇对接至gp41上的疏水口袋，发现了许多可能的结合模式。通过分子动力学模拟和MM-PBSA计算获得了详细的OLE-gp41结合相互作用和结合自由能。我们预测的OLE/gp41复合物中的特定分子相互作用被识别出来，并且羟基酪醇被确定为与gp41结合的主要部分。这项计算研究补充了相应的实验研究，并有助于为进一步优化基于OLE的gp41抑制剂建立一个良好的起点。
