氧气和一氧化碳在人血红蛋白迁移过程研究

彭雪; 芦琛璘; 卢滇楠

doi:10.11949/0438-1157.20190862

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氧气和一氧化碳在人血红蛋白迁移过程研究

生物化学工程与技术 | 更新时间：2026-07-24

- 氧气和一氧化碳在人血红蛋白迁移过程研究
- Investigation on migration process of oxygen and carbon monoxide in human hemoglobin
- 化工学报 2020年71卷第2期页码：724-735
- 作者机构：
  
  化学工程联合国家重点实验室，清华大学化学工程系，北京 100084
- 作者简介：
  
  彭雪（1994—），女，博士研究生，px17@mails.tsinghua.edu.cn
  卢滇楠（1978—），男，博士，副教授，ludiannan@tsinghua.edu.cn
- 基金信息：
  
  国家重点研发计划项目(2018YFA0902200);国家自然科学基金项目(21878175)
- DOI：10.11949/0438-1157.20190862
  中图分类号： TQ 028.8
- 收稿：2019-07-30，
  
  修回：2019-09-03，
  
  网络首发：2020-08-14，
  
  纸质出版：2020-02-05
- 稿件说明：
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彭雪, 芦琛璘, 卢滇楠. 氧气和一氧化碳在人血红蛋白迁移过程研究[J]. 化工学报, 2020, 71(2): 724-735

PENG Xue, LU Chenlin, LU Diannan. Investigation on migration process of oxygen and carbon monoxide in human hemoglobin[J]. CIESC Journal, 2020, 71(2): 724-735
彭雪, 芦琛璘, 卢滇楠. 氧气和一氧化碳在人血红蛋白迁移过程研究[J]. 化工学报, 2020, 71(2): 724-735 DOI： 10.11949/0438-1157.20190862.

PENG Xue, LU Chenlin, LU Diannan. Investigation on migration process of oxygen and carbon monoxide in human hemoglobin[J]. CIESC Journal, 2020, 71(2): 724-735 DOI： 10.11949/0438-1157.20190862.

摘要

为了揭示CO和O

竞争性结合人血红蛋白血红素位点的机制及其与人血红蛋白结构转换之间的关系，本文采用全原子分子动力学模拟（MD）结合马尔科夫状态模型（MSMs）研究氧气（O

）和一氧化碳（CO）分子从水溶液迁移进入人血红蛋白四聚体α链和β链的全过程。分子动力学模拟揭示了O

和CO结合α链和β链的稳态结合位点和瞬态结合位点、迁移通道以及α链的结构变化。结果显示，分子模拟不仅仅能够再现全部实验中所观察到的离散Xe结合位点和分子扩散通道，而且揭示了实验中无法观测的瞬态结合位点和多重气体迁移途径。上述结果表明人血红蛋白因其结构柔性所形成的瞬态通道对于气体分子迁移过程的重要性。除此之外，利用MSM和过渡路径理论（TPT）构建了人血红蛋白α链结构变化与气体分子迁移之间的关系，阐释了血红蛋白中影响气体迁移的关键结构及其微观机制。

Abstract

To reveal the relationship between CO and O

competitive binding to the heme site of human hemoglobin (HbA) and its relationship with HbA structural transition

we used all-atom molecular dynamics simulations (MD) combined with Markov state models (MSMs) to study the migration of O

and CO molecules from the aqueous solution into the heme site of α and β chains of HbA. Molecular dy

namics simulations revealed the steady binding sites and instantaneous binding sites to O

and CO of α and β chains of HbA

migration pathways and structural changes of HbA. It is shown that all discrete Xe binding sites and O

migration pathways observed in experiments can be reproduced by molecular dynamics simulations. Molecular dynamics simulations revealed structural changes in the homeostatic binding sites and transient binding sites

migration channels

and alpha chains of O

and CO binding α

and β chains. Above results demonstrate the importance of instantaneous migration pathways formed due to the flexibility of HbA for gas migration. In addition

MSMs and transition path theory(TPT) were used to investigate the conformational transitions among different microstates in α chain

which provides the mechanism between gases migration behavior and HbA conformational transitions.

关键词

Keywords

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