从量子力学/分子力学自由能量模拟中对大豆脂氧酶中的质子合电子转移的基本见解
Pengfei Li1,2, Alexander V Soudackov1,2, Sharon Hammes-Schiffer1,2
1Department of Chemistry, University of Illinois at Urbana-Champaign , 600 South Mathews Avenue, Urbana, Illinois 61801, United States.
Journal of the American Chemical Society
|February 3, 2018
概括
豆氧化酶
科学领域:
- 生物化学和生物物理
- 酵素学
- 计算化学
背景情况:
- 质子合电子转移 (PCET) 反应在生物系统中至关重要.
- 大豆氧酶 (SLO) 催化一种原型的PCET反应,对于理解酶道化至关重要.
- 野生型 (WT) 和双变异型 (DM) SLO的实验动态同位素效应 (KIEs) 提供了关键数据.
研究的目的:
- 通过先进的计算模拟来研究SLO中的PCET反应机制.
- 阐明导致WT和DMSLO之间实验观察到的KIE差异的因素.
- 将结构和电子特性与道效率相关联.
主要方法:
- 使用混合量子/经典 (QM/MM) 自由能量模拟.
- 计算了自由能量表面和平均力 (PMF) 的潜力.
- 分析了影响PCET反应的无和性和静电效应.
主要成果:
- 模拟准确地复制了WT (∼80) 和DM (∼700) SLO的实验KIE.
- 对于WT,PCET反应是外能反应,对于DM则是轻微内能反应.
- 由于扩展腔中的基质结合,DM中的更大的平衡C-O距离显著增加了KIE.
结论:
- 在DM中扩大的结合腔是其较高KIE的主要驱动因素.
- 无电位和局部静电场有助于高效的道化.
- 虽然蛋白质环境有助于基质对齐,但局部静电是PCET和道的关键.
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