Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore.
J Chem Phys. 2010 Apr 7;132(13):131101. doi: 10.1063/1.3360769.
In this paper, we present a detailed dynamics study of the catalytic core domain (CCD) of HIV-1 integrase using both polarized and nonpolarized force fields. The numerical results reveal the critical role of protein polarization in stabilizing Mg(2+) coordination complex in CCD. Specifically, when nonpolarized force field is used, a remarkable drift of the Mg(2+) complex away from its equilibrium position is observed, which causes the binding site blocked by the Mg(2+) complex. In contrast, when polarized force field is employed in MD simulation, HIV-1 integrase CCD structure is stabilized and both the position of the Mg(2+) complex and the binding site are well preserved. The detailed analysis shows the transition of alpha-helix to 3(10)-helix adjacent to the catalytic loop (residues 139-147), which correlates with the dislocation of the Mg(2+) complex. The current study demonstrates the importance of electronic polarization of protein in stabilizing the metal complex in the catalytic core domain of HIV-1 integrase.
在本文中，我们使用极化和非极化力场对 HIV-1 整合酶的催化核心结构域（CCD）进行了详细的动力学研究。数值结果揭示了蛋白质极化在稳定 CCD 中 Mg2+配位复合物中的关键作用。具体来说，当使用非极化力场时，观察到 Mg2+复合物显著偏离其平衡位置的漂移，这导致结合位点被 Mg2+复合物阻塞。相比之下，当在 MD 模拟中使用极化力场时，HIV-1 整合酶 CCD 结构得到稳定，并且 Mg2+复合物的位置和结合位点都得到很好的保留。详细分析表明，与催化环（残基 139-147）相邻的α-螺旋向 3(10)-螺旋的转变，这与 Mg2+复合物的位移相关。目前的研究表明，蛋白质的电子极化在稳定 HIV-1 整合酶催化核心结构域中的金属复合物方面非常重要。
Zotero 插件