摘要
肌红蛋白具有存储和运输人体内双原子小分子的重要生物学功能．实验证实CO在靠近肌红蛋白血红素基团边缘的结合口袋中具有两个不同的方向．在本文中，我们基于从头算QM／MM动力学模拟的方法详细研究了这两个状态（这两种状态分别命名为B1和B2态）．通过与实验测量的红外光谱数据的对比，证实B1和B2态分别对应于Fe…CO（碳原子更加靠近血红素的中心铁原子）和Fe…OC（氧原子更加靠近血红素的中心铁原子），由蛋白以及溶剂对一氧化碳分子造成的量子极化效应是一氧化碳能够稳定持有两个不同状态的主要源动力．我们计算得到的两个不同状态之间的振动频率偏移量为13．1cm-1，与实验测得的11．5cm-1的位移吻合的很好．模拟结果揭示出蛋白周围的溶剂水可以通过在蛋白活性区域施加电场的方式来辅助加强蛋白的生物功能．通过对肌红蛋白每个残基在一氧化碳分子中心位置产生的电场的定量计算，发现了对总电场有较大贡献的一些氨基酸残基，其中包括了一些带电残基以及三个非带电残基（即HIS64，ILE107，和PHE43）．
Myoglobin has important biological functions in storing and transporting small diatomic molecules in human body. Two possible orientations of carbon monoxide （CO） in the heme distal pocket （named as BI and B2 states） of myoglobin have been experimentally indicated. In this study, ab initio quantum mechanics/molecular mechanics （QM/MM） molecular dynamics simulation of CO in myoglobin was carried out to investigate the two possible B states. Our results demonstrate that the B1 and B2 states correspond to Fe... CO （with carbon atom closer to iron center of heme） and Fe... OC （with oxygen atom closer to Fe）, by comparing with the experimental infrared spectrum. QM electrostatic polarization effect on CO brought from the protein and solvent environment is the main driving force, which anchors CO in two distinctive orientations and hinders its rotation. The calculated vibrational frequency shift between the state B1 and B2 is 13.1 cm-1, which is in good agreement with experimental value of 11.5 cm-1. This study also shows that the electric field produced by the solvent plays an important role in assisting protein functions by exerting directional electric field at the active site of the protein, From residue-based electric field decomposition, several residues were found to have most contributions to the total electric field at the CO center, including a few charged residues and three adjacent uncharged polar residues （namely, HIS64, ILE107, and PHE43）. This study provides new physical insights on rational design of enzyme with higher electric field at the active site.
