State key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Rd., Dalian, 116023, PR China.
J Phys Chem B. 2013 May 2;117(17):4789-97. doi: 10.1021/jp312375g. Epub 2013 Apr 16.
In this work, we have investigated in details the origin of the assembly of the DAP12 dimer with only one NKG2C in the activating immunoreceptor complex from thew two aspects of electronic properties and dynamic structures by performing density functional theory (DFT) calculations and molecular dynamics (MD) simulations. In the DFT calculations, we studied the aggregation ability of the NKG2C(TM) with the DAP12(TM) dimer and the DAP12(TM)-DAP12(TM)-NKG2C(TM) complex by analyzing the electrostatic potentials and frontier molecular orbitals (FMOs), and in the MD simulations we mainly investigated the dynamic structures of the DAP12(TM)-DAP12(TM)-NKG2C(TM) complex and its mutants, as well as the tetramer complex consisting of two DAP12(TM) and two NKG2C(TM) helixes without any restriction. Through the studies of the electrostatic potential, the FMOs, and the dynamic structures, we have provided reasonable explanations to some extent for the experimental observation that only one NKG2C can associate with the DAP12 homodimer. The present theoretical results are expected to give valuable information for further studying the assembly between receptors and signaling subunits.
在这项工作中，我们通过进行密度泛函理论（DFT）计算和分子动力学（MD）模拟，从电子性质和动态结构两个方面详细研究了只有一个 NKG2C 的情况下 DAP12 二聚体与激活免疫受体复合物组装的起源。在 DFT 计算中，我们通过分析静电势和前线分子轨道（FMO）研究了 NKG2C(TM)与 DAP12(TM)二聚体和 DAP12(TM)-DAP12(TM)-NKG2C(TM)复合物的聚集能力，在 MD 模拟中，我们主要研究了 DAP12(TM)-DAP12(TM)-NKG2C(TM)复合物及其突变体的动态结构，以及由两个 DAP12(TM)和两个 NKG2C(TM)螺旋组成的无任何限制的四聚体复合物。通过对静电势、FMO 和动态结构的研究，我们在一定程度上为仅一个 NKG2C 可以与 DAP12 同源二聚体结合的实验观察提供了合理的解释。本理论结果有望为进一步研究受体与信号亚基之间的组装提供有价值的信息。
