Division of Medicinal Chemistry & Natural Products, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Curr Opin Pharmacol. 2010 Dec;10(6):723-30. doi: 10.1016/j.coph.2010.09.006. Epub 2010 Oct 8.
Proteins exist not as singular structures with precise coordinates, but rather as fluctuating bodies that move rapidly through an enormous number of conformational substates. These dynamics have important implications for understanding protein function and for structure-based drug design. NMR spectroscopy is particularly well suited to characterize the dynamics of proteins and other molecules in solution at atomic resolution. Here, NMR relaxation methods for characterizing thermal motions on the picosecond-nanosecond (ps-ns) timescale are reviewed. Motion on this timescale can be conveniently captured by the Lipari-Szabo order parameter, S², a bond-specific measure of restriction of motion. Approaches for determining order parameters are discussed, as are recent examples from the literature that link ps-ns dynamics with conformational entropy, allostery, and protein function in general.
蛋白质并非以具有精确坐标的单一结构存在，而是作为快速移动的、处于大量构象亚稳态的动态分子。这些动态变化对理解蛋白质功能和基于结构的药物设计具有重要意义。NMR 光谱特别适合于在原子分辨率下研究溶液中蛋白质和其他分子的动力学。在这里，我们回顾了用于在皮秒-纳秒（ps-ns）时间尺度上描述热运动的 NMR 弛豫方法。Lipari-Szabo 顺序参数 S²可以方便地捕捉这个时间尺度上的运动，它是对运动受限程度的一种键特异性度量。我们讨论了确定顺序参数的方法，以及文献中的最新示例，这些示例将 ps-ns 动力学与构象熵、变构和蛋白质功能联系起来。
