Department of Chemistry, University of Rome La Sapienza, Rome, Italy.
Proteins. 2011 Mar;79(3):867-79. doi: 10.1002/prot.22924. Epub 2010 Dec 22.
By using multiple molecular dynamics (MD) trajectories, a quantitative description of carbon monoxide (CO) migration within crystal of L29F myoglobin mutant (L29F-Mb) was obtained. The aim was to provide a detailed model for ligand diffusion in the protein to be compared to the available L29F-Mb experimental-computational data and to the corresponding model kinetics we previously obtained for photolyzed CO within crystallized wild-type myoglobin (wt-Mb). Results suggest a clear migration pathway from distal pocket to the proximal site, similar to the one observed in wt-Mb, with a relaxation kinetics differing from the wt-Mb one essentially for the escape rate which is much higher in the mutant. Moreover MD data indicated a clear correlation between CO location within the protein and the conformation adopted by Phe29, well matching the available experimental data as obtained by time-resolved X-ray density maps. Such data, further validating the model used in the simulations, point out the subtle mutual effect between ligand diffusion and protein functional motions possibly explaining the observed dramatic variation of CO exit rate in L29F-Mb.
通过使用多个分子动力学（MD）轨迹，获得了一氧化碳（CO）在 L29F 肌红蛋白突变体（L29F-Mb）晶体中迁移的定量描述。目的是为配体在蛋白质中的扩散提供一个详细的模型，以便与可用的 L29F-Mb 实验计算数据以及我们之前为结晶野生型肌红蛋白（wt-Mb）中光解 CO 获得的相应模型动力学进行比较。结果表明，从远端口袋到近端位置存在明显的迁移途径，与在 wt-Mb 中观察到的途径相似，松弛动力学与 wt-Mb 的动力学明显不同，主要是突变体的逃逸率要高得多。此外，MD 数据表明，CO 在蛋白质内的位置与 Phe29 所采用的构象之间存在明显的相关性，与通过时间分辨 X 射线密度图获得的可用实验数据非常吻合。这些数据进一步验证了模拟中使用的模型，指出了配体扩散和蛋白质功能运动之间的微妙相互作用，这可能解释了在 L29F-Mb 中观察到的 CO 出口率的显著变化。
