通过ab initio分子动力学探测的酶活性位点中的动态灵活性和质子转移
Ivaylo Ivanov1, Michael L Klein
1Center for Molecular Modeling, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, USA. iivanov@cmm.chem.upenn.edu
Journal of the American Chemical Society
|March 18, 2005
概括
最初的分子动力学揭示了在酶催化中关键的连接体运动和质子转移. 这项研究提供了对酶的最终催化步骤和去质子化能量的洞察.
科学领域:
- 生物化学和分子生物学
- 计算化学计算化学
- 酶学 是一种酶学.
背景情况:
- 氨酸酶是尿素循环中至关重要的金属酶,催化L-氨酸到L-ornithine和尿素的水解.
- 活动地点有一个桥梁双核金属集群,对催化活动至关重要,但其动态灵活性仍然不完全理解.
研究的目的:
- 通过使用ab initio分子动力学 (AIMD) 来研究酶活性位点中桥梁双核结构图案的动态灵活性.
- 阐明连接体运动和质子转移在酶的催化机制中的作用,特别是最后一步.
主要方法:
- 开始分子动力学 (AIMD) 模拟被用于研究阿尔金纳的动态行为.
- 分析的重点是第一联体的运动,包括化和桥接碳酸盐.
- 约束分子动力学被用来比较deprotonation自由能量.
主要成果:
- 通过AIMD模拟,可以直接了解第一联体的运动,并揭示了结合模式的动态转换和变化 (例如,Asp234的碳酸盐转移).
- 观察了从桥接核向Asp128的质子转移,并绘制了相关的自由能量表面.
- 桥接核的脱质子自由能量在原生和金属贫的氨酶之间有所不同.
结论:
- 这项研究提供了对酶活性位点的动态灵活性和连接体运动在催化中的关键作用的宝贵见解.
- 观察到的质子转移机制照亮了催化循环的最后一步.
- 脱化自由能量的差异突出了金属离子对酶功能的影响.
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