Extended molecular dynamics simulation of the carbon monoxide migration in sperm whale myoglobin
Extended molecular dynamics simulation of the carbon monoxide migration in sperm whale myoglobin
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DOI：
10.1529/biophysj.103.037432
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发表时间：
2004-06-01
影响因子：
3.4
通讯作者：
Di Nola, A
中科院分区：
文献类型：
--
作者：
Bossa, C;Anselmi, M;Di Nola, A
我们报告了一个扩展的分子动力学模拟野生型抹香鲸肌红蛋白的光解一氧化碳的迁移的结果。我们的研究结果允许以下一个可能的配体迁移动力学从远端口袋的Xe 1腔通过一个路径，涉及其他氙结合腔和瞬间两个额外的包装缺陷沿着的途径。与最近的时间分辨的结构数据与亚纳秒到毫秒分辨率劳厄晶体学的比较显示出更令人满意的协议。事实上，根据时间分辨晶体学，CO在光解后可以占据Xe 1和Xe 4腔。然而，没有关于配体从远端口袋到Xe 1的轨迹的信息。我们的研究结果清楚地显示了蛋白质中的一条可能路径。此外，虽然我们的数据是指一个单一的轨迹，在每个腔中的配体的局部动力学是充分平衡，以获得当地的结构和热力学信息无法访问晶体学。特别是，我们表明，CO运动和蛋白质的波动是严格相关的：相邻腔之间的迁移的自由能计算表明，迁移不是一个简单的扩散，而是动力学或动力学驱动的集体运动的蛋白质;相反地，蛋白质的波动受配体的影响，相邻空腔之间通道的闭合与其附近CO的存在严格相关。时间分辨的晶体学实验和分子动力学模拟之间的兼容性铺平了道路，以更深入地了解内部动力学和包装缺陷的作用，在血红素蛋白的配体结合的控制。
We report the results of an extended molecular dynamics simulation on the migration of photodissociated carbon monoxide in wild-type sperm whale myoglobin. Our results allow following one possible ligand migration dynamics from the distal pocket to the Xe1 cavity via a path involving the other xenon binding cavities and momentarily two additional packing defects along the pathway. Comparison with recent time resolved structural data obtained by Laue crystallography with subnanosecond to millisecond resolution shows a more than satisfactory agreement. In fact, according to time resolved crystallography, CO, after photolysis, can occupy the Xe1 and Xe4 cavities. However, no information on the trajectory of the ligand from the distal pocket to the Xe1 is available. Our results clearly show one possible path within the protein. In addition, although our data refer to a single trajectory, the local dynamics of the ligand in each cavity is sufficiently equilibrated to obtain local structural and thermodynamic information not accessible to crystallography. In particular, we show that the CO motion and the protein fluctuations are strictly correlated: free energy calculations of the migration between adjacent cavities show that the migration is not a simple diffusion but is kinetically or thermodynamically driven by the collective motions of the protein; conversely, the protein fluctuations are influenced by the ligand in such a way that the opening/closure of the passage between adjacent cavities is strictly correlated to the presence of CO in its proximity. The compatibility between time resolved crystallographic experiments and molecular dynamics simulations paves the way to a deeper understanding of the role of internal dynamics and packing defects in the control of ligand binding in heme proteins.