National Renewable Energy Laboratory , MS ESIF301, 15013 Denver West Parkway, Golden, Colorado 80401, United States.
J Phys Chem B. 2014 Jan 30;118(4):890-900. doi: 10.1021/jp408621r. Epub 2014 Jan 21.
To better understand the proton transport through the H2 production catalysts, the [FeFe] hydrogenases, we have undertaken a modeling and simulation study of the proton transfer processes mediated by amino acid side-chain residues in hydrogenase I from Clostridium pasteurianum. Free-energy calculation studies show that the side chains of two conserved glutamate residues, Glu-279 and Glu-282, each possess two stable conformations with energies that are sensitive to protonation state. Coordinated conformational changes of these residues can form a proton shuttle between the surface Glu-282 and Cys-299, which is the penultimate proton donor to the catalytic H-cluster. Calculated acid dissociation constants are consistent with a proton relay connecting the H-cluster to the bulk solution. The complete proton-transport process from the surface-disposed Glu-282 to Cys-299 is studied using coupled semiempirical quantum-mechanical/classical-mechanical dynamics. Two-dimensional free-energy maps show the mechanisms of proton transport, which involve Glu-279, Ser-319, and a short internal water relay to connect functionally Glu-282 with the H-cluster. The findings of conformational bistability, PT event coupling with pKa mismatch, and water participation have implications in the design of artificial water reduction or general electrocatalytic H2-production catalysts.
为了更好地理解质子在 H2 生产催化剂[FeFe]氢化酶中的传输过程，我们对来自巴氏梭菌的氢化酶 I 中氨基酸侧链残基介导的质子转移过程进行了建模和模拟研究。自由能计算研究表明，两个保守的谷氨酸残基 Glu-279 和 Glu-282 的侧链各有两种稳定的构象，其能量对质子化状态敏感。这些残基的协调构象变化可以在表面 Glu-282 和 Cys-299 之间形成质子穿梭，Cys-299 是催化 H 簇的倒数第二个质子供体。计算得到的酸离解常数与连接 H 簇和体相溶液的质子传递体一致。使用耦合半经验量子力学/经典力学动力学研究了从表面排布的 Glu-282 到 Cys-299 的完整质子传输过程。二维自由能图谱显示了质子传输的机制，涉及 Glu-279、Ser-319 和一个短的内部水接力，将功能上的 Glu-282 与 H 簇连接起来。构象双稳定性、PT 事件与 pKa 不匹配的耦合以及水的参与，对人工水还原或一般电催化 H2 生产催化剂的设计具有重要意义。
