Sussman Fredy, Villaverde M Carmen, Martínez Luis
Departamento de Química Orgánica, Facultad de Química, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
Protein Eng. 2002 Sep;15(9):707-11. doi: 10.1093/protein/15.9.707.
One of the most successful drug targets against AIDS in the last decade has been the HIV-1 protease (HIV-1 PR), an enzyme that processes the polyprotein gene products into active replicative viral proteins. In our quest for a wide-ranging, binding free energy function we have extended the solvent accessibility free energy predictor (SAFE_p) method, recently developed for peptidic HIV-1 PR inhibitors, to the study of the binding of cyclic urea (CU) HIV-1 PR inhibitors. Our results show that there is a need for a specific term depicting polar contacts to be added to the original SAFE_p analytical expression, an outcome not seen in our studies of HIV-1 PR peptidic inhibitors. Nevertheless, despite the higher profile of the electrostatic interactions in the binding of the CU inhibitors, our analysis indicates that CU inhibitor binding is still driven by the hydrophobic entropic contribution, as much as for the peptidic inhibitors.
过去十年中，最成功的抗艾滋病药物靶点之一是HIV-1蛋白酶（HIV-1 PR），该酶将多聚蛋白基因产物加工成具有活性的复制性病毒蛋白。在寻求一种广泛适用的结合自由能函数时，我们将最近为肽类HIV-1 PR抑制剂开发的溶剂可及性自由能预测器（SAFE_p）方法扩展到了环脲（CU）HIV-1 PR抑制剂结合的研究中。我们的结果表明，需要在原始的SAFE_p分析表达式中添加一个描述极性接触的特定项，这一结果在我们对HIV-1 PR肽类抑制剂的研究中并未出现。然而，尽管在CU抑制剂结合中静电相互作用更为突出，但我们的分析表明，与肽类抑制剂一样，CU抑制剂的结合仍然是由疏水熵贡献驱动的。
