Specific parametrisation of a hybrid potential to simulate reactions in phosphatases
Specific parametrisation of a hybrid potential to simulate reactions in phosphatases
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DOI：
10.1039/b511805k
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发表时间：
2006-01-21
影响因子：
3.3
通讯作者：
Loos, M
中科院分区：
文献类型：
--
作者：
Arantes, GM;Loos, M
磷酸酶是关键的生物分子，因为它们调节许多细胞过程。这些酶已经被研究了很多年，但对催化机制仍然存在疑问。计算机模拟可以用来阐明这些问题。在这里，我们开发了一个新的和具体的parametrisation，并提出了广泛的测试的混合潜力，可用于可靠地模拟磷酸酶催化的反应。在训练集中使用磷酸酯硫解和醇解的高水平从头算数据。参数化量子力学哈密顿再现从头能量与3千卡摩尔（-1）的均方根偏差的物种沿着各种磷酸酯反应的途径。用磷酸酶VHR催化的校准杂化势进行模拟的初步结果表明，计算的反应势垒与实验符合得很好。
Phosphatases are key biomolecules because they regulate many cellular processes. These enzymes have been studied for many years, but there are still doubts about the catalytic mechanism. Computer simulations can be used to shed light on these questions. Here we develop a new and specific parametrisation, and present extensive tests of a hybrid potential that can be used to reliably simulate reactions catalysed by phosphatases. High level ab initio data for phosphate ester thiolysis and alcoholysis is used in the training set. The parametrised quantum mechanical Hamiltonian reproduces ab initio energies with a root mean-squared deviation of 3 kcal mol(-1) for species along the pathway of various phosphate ester reactions. Preliminary results for simulation with the calibrated hybrid potential of catalysis by the phosphatase VHR indicate the calculated reaction barriers are in very good agreement with experiment.