期刊
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
卷 8, 期 11, 页码 4637-4645出版社
AMER CHEMICAL SOC
DOI: 10.1021/ct300329h
关键词
-
资金
- EPSRC [EP/G007705/01]
- EPSRC
- EPSRC under the CCP-BioSim project [EP/J010588/1]
- Engineering and Physical Sciences Research Council [EP/J010588/1, EP/G007705/1] Funding Source: researchfish
- EPSRC [EP/G007705/1, EP/J010588/1] Funding Source: UKRI
Density functional theory (DFT) based quantum mechanical/molecular mechanical (QM/MM) calculations have provided valuable insight into the reactivity of the cytochrome P450 family of enzymes (P450s). A failure of commonly used DFT-methods, such as B3LYP, is the neglect of dispersion interactions An empirical dispersion correction has been shown to improve the accuracy of gas phase DFT calculations of P450s. The current work examines the effect of the dispersion correction in QM/MM calculations on P450s. The hydrogen abstraction from camphor, and hydrogen abstraction and C-O addition of cydohexene and propene by P450(cam), have been modeled, along with the addition of benzene to Compound I in CYP2C9, at the B3LYP-D2/CHARMM27 level of theory. Single point energy calculations were also performed at the B3LYP-D3//B3LYP-D2/CHARMM27 level. The dispersion corrections lower activation energy barriers significantly (by similar to 5 kcal/mol), as seen for gas phase calculations, but has a small effect on optimized geometries These effects are likely to be important in modeling reactions catalyzed by other enzymes also Given the low computational cost of including such dispersion corrections, we recommend doing so in all B3LYP based QM/MM calculations.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据