Key Laboratory of Industrial Biocatalysis, Ministry of Education, China.
Phys Chem Chem Phys. 2017 May 10;19(18):11690-11697. doi: 10.1039/c7cp00887b.
Molecular dynamics (MD) simulations, in combination with the Markov-state model (MSM), were applied to probe CO diffusion from an aqueous solution into the active site of human carbonic anhydrase II (hCA-II), an enzyme useful for enhanced CO capture and utilization. The diffusion process in the hydrophobic pocket of hCA-II was illustrated in terms of a two-dimensional free-energy landscape. We found that CO diffusion in hCA-II is a rate-limiting step in the CO diffusion-binding-reaction process. The equilibrium distribution of CO shows its preferential accumulation within a hydrophobic domain in the protein core region. An analysis of the committors and reactive fluxes indicates that the main pathway for CO diffusion into the active site of hCA-II is through a binding pocket where residue Gln contributes to the maximal flux. The simulation results offer a new perspective on the CO hydration kinetics and useful insights toward the development of novel biochemical processes for more efficient CO sequestration and utilization.
分子动力学（MD）模拟结合马尔可夫状态模型（MSM）被应用于探究 CO 从水溶液扩散进入人碳酸酐酶 II（hCA-II）活性中心的过程，该酶在增强 CO 捕获和利用方面具有重要作用。通过二维自由能景观图描绘了 hCA-II 疏水性口袋中的扩散过程。我们发现，CO 在 hCA-II 中的扩散是 CO 扩散-结合-反应过程中的限速步骤。CO 的平衡分布表明其优先聚集在蛋白质核心区域的疏水区内。对触变物和反应通量的分析表明，CO 扩散进入 hCA-II 活性中心的主要途径是通过一个结合口袋，其中残基 Gln 对最大通量有贡献。模拟结果为 CO 水合动力学提供了新的视角，并为开发更有效的 CO 捕获和利用的新型生化过程提供了有用的见解。
