Orlowski Slawomir, Nowak Wieslaw
Theoretical Molecular Biophysics Group, Institute of Physics, Nicolaus Copernicus University, ul. Grudziadzka 5, 87-100, Torun, Poland.
J Mol Model. 2007 Jul;13(6-7):715-23. doi: 10.1007/s00894-007-0203-x. Epub 2007 May 15.
Cytoglobin (Cyg)--a new member of the vertebrate heme globin family--is expressed in many tissues of the human body but its physiological role is still unclear. It may deliver oxygen under hypoxia, serve as a scavenger of reactive species or be involved in collagen synthesis. This protein is usually six-coordinated and binds oxygen by a displacement of the distal HisE7 imidazole. In this paper, the results of 60 ns molecular dynamics (MD) simulations of dioxygen diffusion inside Cyg matrix are discussed. In addition to a classical MD trajectory, an approximate Locally Enhanced Sampling (LES) method has been employed. Classical diffusion paths were carefully analyzed, five cavities in dynamical structures were determined and at least four distinct ligand exit paths were identified. The most probable exit/entry path is connected with a large tunnel present in Cyg. Several residues that are perhaps critical for kinetics of small gaseous diffusion were discovered. A comparison of gaseous ligand transport in Cyg and in the most studied heme protein myoglobin is presented. Implications of efficient oxygen transport found in Cyg to its possible physiological role are discussed.
细胞红蛋白（Cyg）——脊椎动物血红素球蛋白家族的新成员——在人体的许多组织中都有表达，但其生理作用仍不清楚。它可能在缺氧情况下输送氧气，充当活性物质的清除剂，或参与胶原蛋白的合成。这种蛋白质通常是六配位的，通过远端HisE7咪唑的取代来结合氧气。本文讨论了Cyg基质内双氧扩散的60纳秒分子动力学（MD）模拟结果。除了经典的MD轨迹外，还采用了一种近似的局部增强采样（LES）方法。仔细分析了经典扩散路径，确定了动态结构中的五个腔，并识别出至少四条不同的配体出口路径。最可能的进出路径与Cyg中存在的一个大通道相连。发现了几个可能对小气体扩散动力学至关重要的残基。本文还比较了Cyg和研究最多的血红素蛋白肌红蛋白中的气态配体运输。讨论了Cyg中高效氧气运输对其可能的生理作用的影响。
