Modeling biotransformation reactions by combined quantum mechanical/molecular mechanical approaches: from structure to activity.
Modeling biotransformation reactions by combined quantum mechanical/molecular mechanical approaches: from structure to activity.
复制标题
通过结合量子力学/分子力学方法来模拟生物转化反应：从结构到活性。
DOI：
10.2174/1568026033452005
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发表时间：
2003
影响因子：
3.4
通讯作者：
A. Mulholland
中科院分区：
文献类型：
--
作者：
L. Ridder;A. Mulholland
综述了量子力学/分子力学（QM/MM）方法及其在生物转化酶和药物代谢研究中的应用。在过去的十年中，模拟酶反应的理论方法得到了迅速发展。特别是，QM/MM方法提供了对酶催化反应的详细见解，这在补充实验研究方面非常有价值。QM/MM方法允许在量子力学水平上研究酶的活性位点中的反应基团，而周围的蛋白质和溶剂则包括在经典的（计算成本较低的）分子力学水平上。现有的QM/MM实现在QM和MM区域之间的交互级别以及设置到QM和MM区域的分区的方式方面有所不同。一些一般性的考虑有关的反应建模进行了讨论，并描述了一些QM/MM研究与药物代谢。这些研究表明，重要的代谢反应的理论建模提供了详细的见解，反应机制和酶残留物的特定催化作用，以及解释不同代谢物的转化率的变化。这些信息是必不可少的方法来预测药物代谢的发展，并了解生物转化酶的遗传多态性的代谢效应。
An overview of the combined quantum mechanical/molecular mechanical (QM/MM) approach and its application to studies of biotransformation enzymes and drug metabolism is given. Theoretical methods to simulate enzymatic reactions have rapidly developed during the last decade. In particular, QM/MM methods provide detailed insights into enzyme catalyzed reactions, which can be extremely valuable in complementing experimental research. QM/MM methods allow the reacting groups in the active site of an enzyme to be studied at a quantum mechanical level, while the surrounding protein and solvent is included at a classical (and computationally less expensive) molecular mechanical level. Existing QM/MM implementations vary in the level of interaction between the QM and MM regions and in the way the partitioning into QM and MM regions is setup. Some general considerations concerning reaction modeling are discussed and a number of QM/MM studies related to drug metabolism are described. These studies illustrate that theoretical modeling of important metabolic reactions provides detailed insights into mechanisms of reaction and specific catalytic effects of enzyme residues as well as explaining variation in rates of conversion of different metabolites. Such information is essential in the development of methods to predict metabolism of drugs and to understand metabolic effects of genetic polymorphism in biotransformation enzymes.
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DOI：
10.1016/s0021-9258(18)42831-1
发表时间：
1992-03
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Suxing Liu;Pinghui Zhang;Xinhua Ji;William W. Johnson;G. Gilliland;Richard N. Armstrong
通讯作者：
Suxing Liu;Pinghui Zhang;Xinhua Ji;William W. Johnson;G. Gilliland;Richard N. Armstrong
睾丸 20 α-羟基类固醇脱氢酶的分子克隆：与醛糖还原酶的同一性。
影响因子：
2.9
作者：
Warren,JC;Murdock,GL;Ma,Y;Goodman,SR;Zimmer,WE
通讯作者：
Zimmer,WE
影响因子：
7.3
作者：
Díaz, N;Suárez, D;Merz, KM
通讯作者：
Merz, KM
DOI：
10.1016/s0021-9258(19)47379-1
发表时间：
1991-09
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
B. Entsch;B. Palfey;D. Ballou;Vincent Massey
通讯作者：
B. Entsch;B. Palfey;D. Ballou;Vincent Massey
影响因子：
2.9
作者：
Pinghui Zhang;Suxing Liu;Shu-ou Shan;Xinhua Ji;Gary L. Gilliland;Richard N. Armstrong
通讯作者：
Pinghui Zhang;Suxing Liu;Shu-ou Shan;Xinhua Ji;Gary L. Gilliland;Richard N. Armstrong