氧化与铁胺结合:计算机模拟调查
Andresa Messias1, Andrea Pasquadibisceglie2, Diego Alonso de Armiño1
1Facultad de Ciencias Exactas y Naturales, Departamento de Química Inorgánica, Analítica y Química Física, Universidad de Buenos Aires, Intendente Güiraldes 2160, C1428EHA Buenos Aires, Argentina; CONICET - Universidad de Buenos Aires, Instituto de Química-Física de los Materiales, Medio Ambiente y Energía (INQUIMAE), Ciudad Universitaria, Pabellón 2, C1428EHA Buenos Aires, Argentina.
Journal of inorganic biochemistry
|August 12, 2023
概括
尼特罗宾丁 (Nbs) 由于铁原子移位而表现出缓慢的氧化 (NO) 结合,而不是连接体迁移障碍. NO 结合也会触发His-Fe 键的转移,与水分子形成稳定的替代形态.
科学领域:
- 生物化学和分子生物学
- 计算生物物理学的计算生物物理学
背景情况:
- 尼特罗宾丁 (Nbs) 是保存的血红蛋白与暴露的血红铁.
- 尽管远程可访问,但Nbs表现出比肌球蛋白 (Mbs) 更慢的配体结合动力学.
- 与Nbs结合的氧化 (NO) 会削弱或裂开近端的胺铁结合.
研究的目的:
- 为了阐明在Nitrobindins中的连接体结合动力学背后的分子机制.
- 为了研究连接物迁移和结合形成在NO结合中的作用.
- 为了了解NO相互作用时的近端胺-铁键动态.
主要方法:
- 经典分子动力学模拟与指导分子动力学.
- 根据Jarzinski的等式来计算连接体迁移的自由能量概况.
- 量子古典 (QM-MM) 对His-Fe键动态的优化.
主要成果:
- 在Nbs中连接体的迁移在很大程度上不受阻碍.
- 结合的主要障碍是铁原子从血平面的显著移位.
- NO 结合会诱导近端胺的稳定替代形态,与水分子相互作用.
结论:
- 在Nbs中NO结合率缓慢的原因是铁原子的移位,而不是连接体的迁移.
- 计算机模拟揭示了在NO结合时改变的His-Fe键稳定性的结构基础.
- 在Nbs.中确定了近接胺的水媒介替代构造.
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