半胱氨酸双加氧酶催化机制的QM/MM-TDDFT研究

半胱氨酸双加氧酶催化的半胱氨酸氧化过程是典型的两态反应，反应中涉及自旋反转、需要考虑旋轨耦合作用。目前，常采用基于密度泛函的△SCF方法研究两态反应；但这一方法有理论缺陷，应用于开壳层体系受限，且没有考虑旋轨耦合作用，所以各个自旋态的相对能量估算不好。 本项目拟构建可用于复杂生命体系两态反应研究的QM/MM-TDDFT方法。首先，采用Spin-adapted TDDF方法突破Spin-conserving TDDFT方法的限制，从而可计算多个自旋态的相对能量；然后，采用sf-X2C-S-TD-DFT-SOC方法考虑旋轨耦合作用；最后，将TDDFT与QM/MM方法结合实现复杂生命体系的理论计算。拟在对TDDFT方法进行改进的基础上编写程序联合调用BDF和QM4D程序包实现方案，并应用于研究半胱氨酸双加氧酶催化反应及其模型配合物氧气激活过程，从而达到甄别机理、理解细节和总结规律的研究目的。

The cysteine dioxygenase (CDO) catalyzed reaction process is a typical （two state reactivity）TSR. Currently, The density functional based △SCF method is adopted to calculate relative energies of different spin states. But, the inborn limitation of △SCF method makes it a problem process, which restricts its application in open-shell systems. At the same time, The spin-orbital coupling effect is not counted in the △SCF method. The calculated energy differences are not as good as expected. The motivation of the proposal is to build a QM/MM-TDDFT scheme for TSR of complex life system. Firstly, the Spin-adapted Open-shell TDDFT method is used to conquer the problem of spin-conserving TDDFT method and to generate correct spin states. Secondly, sf-X2C-S-TD-DFT-SOC method is used to evaluate the spin-orbital coupling effect. Finally, the TDDFT method is combined to QM/MM approach which gives TDDFT ability of application on complex life system. The TDDFT method will be tested and improved before it is used in QM/MM-TDDFT approach. We prefer to combine BDF and QM4D packages and write relevant codes in order to achieve the function. Furthermore, The QM/MM-TDDFT scheme will be applied in calculating the two state reaction mechanism of CDO and bio mimic CDO models.