Department of Chemistry, Princeton University, Princeton, NJ, 08544, USA.
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, 14850, USA.
Nat Commun. 2020 Mar 9;11(1):1271. doi: 10.1038/s41467-020-14933-6.
Protein dynamics are integral to biological function, yet few techniques are sensitive to collective atomic motions. A long-standing goal of X-ray crystallography has been to combine structural information from Bragg diffraction with dynamic information contained in the diffuse scattering background. However, the origin of macromolecular diffuse scattering has been poorly understood, limiting its applicability. We present a finely sampled diffuse scattering map from triclinic lysozyme with unprecedented accuracy and detail, clearly resolving both the inter- and intramolecular correlations. These correlations are studied theoretically using both all-atom molecular dynamics and simple vibrational models. Although lattice dynamics reproduce most of the diffuse pattern, protein internal dynamics, which include hinge-bending motions, are needed to explain the short-ranged correlations revealed by Patterson analysis. These insights lay the groundwork for animating crystal structures with biochemically relevant motions.
蛋白质动力学是生物功能的重要组成部分，但很少有技术能够灵敏地探测到原子的整体运动。X 射线晶体学的一个长期目标是将布拉格衍射的结构信息与漫散射背景中包含的动态信息结合起来。然而，由于对大分子漫散射的起源缺乏了解，限制了其应用。我们呈现了来自三方晶系溶菌酶的精细采样漫散射图谱，具有前所未有的准确性和细节，清晰地分辨出分子间和分子内的相关性。这些相关性使用全原子分子动力学和简单的振动模型进行了理论研究。尽管晶格动力学可以再现大部分漫散射模式，但需要蛋白质内部动力学（包括铰链弯曲运动）来解释 Patterson 分析所揭示的短程相关性。这些见解为用具有生物化学相关性的运动来模拟晶体结构奠定了基础。
