General transition-state force field for cytochrome p450 Hydroxylation
General transition-state force field for cytochrome p450 Hydroxylation
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DOI：
10.1021/ct700110f
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发表时间：
2007-09-01
影响因子：
5.5
通讯作者：
Ryde, Ulf
中科院分区：
文献类型：
--
作者：
Rydberg, Patrik;Olsen, Lars;Ryde, Ulf
我们用Q2 MM方法计算了细胞色素P450催化脂肪羟化的吸氢过渡态的力场参数。该参数化是基于24个不同衬底模型的量子化学(B3LYP)过渡态结构和海森矩阵(14个在训练集，10个在测试集中)。通过对底物使用一般的琥珀力场(GAFF)，该力场旨在适用于任何类药物分子。这些参数分别在0.1埃和1.2度内再现了键长度和角度的几何图形，训练集和测试集之间没有显著差异。海森矩阵的重现性也很好，相关系数为0.99。参数化是由Norrby和Liljefors的理想迭代方法执行的，我们已经为Amber软件实现了这种方法。
We have developed force-field parameters for the hydrogen-abstraction transition state of aliphatic hydroxylation by cytochrome P450 using the Q2MM approach. The parametrization is based on quantum chemical (B3LYP) transition-state structures and Hessian matrices for 24 diverse substrate models (14 in the training set and 10 in the test set). The force field is intended to be applicable to any druglike molecule by the use of the general Amber force field (GAFF) for the substrates. The parameters reproduce the geometries within 0.1 angstrom and 1.2 degrees for bond lengths and angles, respectively, with no significant differences between the training and test sets. The Hessian matrix is also well reproduced with a correlation coefficient of 0.99. The parametrization is performed by the ideal iterative approach of Norrby and Liljefors, which we have implemented for the Amber software.