Department of Experimental Therapeutics, MD Anderson Cancer Center, Houston, Texas 77030, United States.
J Chem Inf Model. 2011 Sep 26;51(9):2352-60. doi: 10.1021/ci2001742. Epub 2011 Aug 25.
Molecular docking is often performed with rigid receptors. This can be a serious limitation, since the receptor often differs between bound and unbound forms or between bound forms with different ligands. We recently developed a normal-mode based docking method and showed that it is possible to obtain reasonable estimates of the complexed form of the pleckstrin homology (PH) domain of Akt, starting with the free form of the receptor. With inositol (1,3,4,5)-tetrakisphosphate (IP4) as the ligand the docked results agree with the known high-resolution X-ray crystal structure of the IP4-Akt PH domain complex. We also tested our methods with PH4, SC66, and PIT-1, several recently designed PH domain inhibitors. The results are shown to be consistent with available experimental data and previous modeling studies. The method we described can be used for molecular docking analysis even when only an approximation of the experimental structure or model is known.
分子对接通常使用刚性受体进行。这可能是一个严重的限制，因为受体在结合和未结合形式之间或具有不同配体的结合形式之间通常会有所不同。我们最近开发了一种基于正常模式的对接方法，并表明可以从受体的自由形式开始，获得 Akt 的pleckstrin 同源（PH）结构域与配体结合的合理估计。使用肌醇（1,3,4,5）-四磷酸（IP4）作为配体，对接结果与已知的高分辨率 X 射线晶体结构 Akt PH 结构域复合物一致。我们还使用 PH4、SC66 和 PIT-1 等几种最近设计的 PH 结构域抑制剂对我们的方法进行了测试，结果与可用的实验数据和以前的建模研究一致。当仅知道实验结构或模型的近似值时，我们描述的方法也可用于分子对接分析。
