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

作　　者：彭雪 芦琛璘 卢滇楠[1] PENG Xue;LU Chenlin;LU Diannan(State Key Laboratory of Chemical Engineering,Department of Chemical Engineering,Tsinghua University,Beijing 100084,China)

机构地区：[1]化学工程联合国家重点实验室清华大学化学工程系

出　　处：《化工学报》2020年第2期724-735,共12页CIESC Journal

基　　金：国家重点研发计划项目(2018YFA0902200);国家自然科学基金项目(21878175)

摘　　要：为了揭示CO和O2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(O2)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O2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。To reveal the relationship between CO and O2 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 O2 and CO molecules from the aqueous solution into the heme site ofαandβchains of HbA.Molecular dynamics simulations revealed the steady binding sites and instantaneous binding sites to O2 and CO ofαandβchains of HbA,migration pathways and structural changes of HbA.It is shown that all discrete Xe binding sites and O2 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 O2 and CO bindingaandbchains.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 inαchain,which provides the mechanism between gases migration behavior and HbA conformational transitions.

关 键 词：人血红蛋白 血红素 氧气 一氧化碳 分子模拟 马尔科夫状态模型 气体迁移 

分 类 号：TQ028.8[化学工程]