Dipartimento di Fisica e Scienze della Terra, Università degli Studi di Parma, viale delle Scienze 7A, 43124, Parma, Italy.
Phys Chem Chem Phys. 2013 Jul 14;15(26):10686-701. doi: 10.1039/c3cp51149a. Epub 2013 Jun 3.
The presence of cavities and tunnels in the interior of proteins, in conjunction with the structural plasticity arising from the coupling to the thermal fluctuations of the protein scaffold, has profound consequences on the pathways followed by ligands moving through the protein matrix. In this perspective we discuss how quantitative analysis of experimental rebinding kinetics from laser flash photolysis, trapping of unstable conformational states by embedding proteins within the nanopores of silica gels, and molecular simulations can synergistically converge to gain insight into the migration mechanism of ligands. We show how the evaluation of the free energy landscape for ligand diffusion based on the outcome of computational techniques can assist the definition of sound reaction schemes, leading to a comprehensive understanding of the broad range of chemical events and time scales that encompass the transport of small ligands in hemeproteins.
蛋白质内部的腔和隧道的存在，加上与蛋白质支架热波动的耦合所产生的结构可塑性，对配体在蛋白质基质中移动所遵循的途径有深远的影响。在这个观点中，我们讨论了如何通过定量分析激光闪光光解的实验再结合动力学、通过将蛋白质嵌入硅胶纳米孔中来捕获不稳定的构象状态，以及分子模拟，可以协同收敛，以深入了解配体的迁移机制。我们展示了如何基于计算技术的结果评估配体扩散的自由能景观，以协助确定合理的反应方案，从而全面理解包含小分子配体在血红素蛋白中运输的广泛化学事件和时间尺度。
