理论研究电子极化在酶催化功能中的作用

In this project, we plan to systematically study a series of enzymatic systems that play important role in biological functions, utilizing our newly developed hybrid ab initio quantum mechanical and molecular mechanical method (ai-QM/MM-ppc). In treating protein electronic polarization, recently we have made major progress in this direction by successfully bridging the ai-QM/MM method and the polarized protein-specific charges(PPC). We will apply the ai-QM/MM-ppc method to the studies of enzyme catalysis by focusing on ellucidating the effects of electronic polarization on catalytic mechanism, particularly its role in lowering the reaction barrier to accelerate the reaction process or changing the reaction transition state. Also we will introduce the contrained density functional theory (CDFT) into our ai-QM/MM-ppc method in order to enhance its capability in treating the active center of enzymes and increasing the accuracy of energy calculation. The enzymatic systems we plan to investigate include 1) subtilisin，2）human DNA polymerase beta,3)carbonic anhydrase and 4）ribosome.

在本项目中，我们将利用最新发展的基于从头计算和电子极化的量子力学和分子力学的组合方法(ai-QM/MM-ppc)，对一系列在生物体内起重要作用的酶体系进行系统而细致的模拟计算分析。在处理蛋白电子极化方面，我们成功实现了QM/MM与蛋白特定极化电荷（PPC）的对接。我们将利用此方法上的优势，在对酶催化机制的理论研究中重点探索电子极化对其催化作用的影响，如研究电子极化能否降低化学反应能垒从而加速反应的进程或改变反应的过渡态等。另外，我们还将引入带约束的密度泛函理论方法(CDFT)，从而增强QM/MM处理酶反应活性中心并提高能量计算准确度的能力。我们计划研究的生物酶体系包括1）subtilisin，2）human DNA polymerase beta,3)carbonic anhydrase 和4）ribosome.