内部自由度,结构动机,和5'-deoxyadenosyl基的构造能量学:影响功能在腺基巴胺依赖的酶. 一个计算研究研究
Dmitry V Khoroshun1, Kurt Warncke, Shyue-Chu Ke
1Cherry L. Emerson Center for Scientific Computation, Department of Chemistry, Emory University, Atlanta, Georgia 30322, USA.
Journal of the American Chemical Society
|January 9, 2003
概括
计算研究表明,虽然5 5
科学领域:
- 计算化学的计算化学
- 生物物理化学 生物物理化学
- 量子化学 是一个量子化学.
背景情况:
- 5'-脱氧亚丁基是生物系统内基质化学中的关键中间体,特别是在依赖辅酶B12的酶中.
- 了解其潜在能量表面对于阐明反应机制和酶功能至关重要.
研究的目的:
- 通过计算来探索气相中自由5'-脱氧亚丁基的潜在能量表面.
- 识别关键的相互作用和结构变化,决定其反应性和稳定性.
- 为了将计算发现与阿登索科巴胺的实验观测相关联.
主要方法:
- 密度函数理论 (DFT) 和第二阶梅勒-普莱塞特扰动理论 (MP2).
- 使用6-31G(d) 和6-31++G(d,p) 基数组进行计算.
- 吸引力和排斥力相互作用的分析,包括键和固体效应.
主要成果:
- 5',8循环化途径在能量上是有利的 (外热的约为20 kcal/mol),但在动力上受到阻碍.
- 基团和氨酸N3之间的键是开放异构体中显著的吸引力.
- 由于排斥性和吸引性相互作用,利博-氨酸旋转显著影响能量.
结论:
- 糖键旋转可能是酶中长距离基因迁移的主要因素.
- 甘氨基基旋转和Co-C键裂变之间的协同作用可以解释adenosylcobalamin中的labilization.
- 蛋白质环境的影响需要进一步研究.
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