Department for NMR-based Structural Biology, Max-Planck Institute for Biophysical Chemistry, Am Fassberg 11, D-37077 Göttingen, Germany.
Molecules. 2013 Sep 26;18(10):11904-37. doi: 10.3390/molecules181011904.
Nuclear Magnetic Resonance (NMR) spectroscopy is a powerful tool that has enabled experimentalists to characterize molecular dynamics and kinetics spanning a wide range of time-scales from picoseconds to days. This review focuses on addressing the previously inaccessible supra-tc window (defined as τ(c) < supra-τ(c) < 40 μs; in which tc is the overall tumbling time of a molecule) from the perspective of local inter-nuclear vector dynamics extracted from residual dipolar couplings (RDCs) and from the perspective of conformational exchange captured by relaxation dispersion measurements (RD). The goal of the first section is to present a detailed analysis of how to extract protein dynamics encoded in RDCs and how to relate this information to protein functionality within the previously inaccessible supra-τ(c) window. In the second section, the current state of the art for RD is analyzed, as well as the considerable progress toward pushing the sensitivity of RD further into the supra-τ(c) scale by up to a factor of two (motion up to 25 μs). From the data obtained with these techniques and methodology, the importance of the supra-τ(c) scale for protein function and molecular recognition is becoming increasingly clearer as the connection between motion on the supra-τ(c) scale and protein functionality from the experimental side is further strengthened with results from molecular dynamics simulations.
核磁共振（NMR）光谱学是一种强大的工具，使实验人员能够表征跨越广泛时间尺度的分子动力学和动力学，从皮秒到天。本综述重点从残留偶极耦合（RDC）中提取的局部核间向量动力学的角度以及通过弛豫分散测量（RD）捕获的构象交换的角度，解决以前无法进入的超 tc 窗口（定义为 τ(c) < supra-τ(c) < 40 μs；其中 tc 是分子的整体旋转时间）。第一部分的目标是详细分析如何从 RDC 中提取编码的蛋白质动力学，以及如何将此信息与超 tc 窗口内的蛋白质功能相关联。在第二部分，分析了 RD 的当前最新技术，并朝着将 RD 的灵敏度进一步推向超 tc 尺度的方向取得了相当大的进展，灵敏度提高了两倍（运动速度高达 25 μs）。通过这些技术和方法获得的数据，以及随着分子动力学模拟的结果进一步加强了超 tc 尺度上的运动与蛋白质功能之间的实验联系，超 tc 尺度对蛋白质功能和分子识别的重要性变得越来越清晰。
