论文标题
分子分子扩散和抗体蛋白与Megahertz X射线自由电子激光脉冲的分子扩散和聚集
Resolving molecular diffusion and aggregation of antibody proteins with megahertz X-ray free-electron laser pulses
论文作者
论文摘要
具有Megahertz重复率的X射线自由电子激光器（XFELS）可以为生物大分子溶液的结构动力学提供新的见解。但是，很高的剂量速率会导致横梁引起的动力学和由于辐射损伤而导致的结构变化。在这里，我们使用Megahertz X射线光子相关光谱（MHz-XPC）在欧洲XFEL上探测致密抗体蛋白（IG-PEG）溶液的动力学。通过改变总剂量和剂量率，我们确定了一种用于测量其第一个配位壳中蛋白质运动的制度，量化XFEL诱导的效果，例如驱动运动，并绘制凝聚动力学的程度。结果表明，对于低于$ 1.06 \，\ mathrm {kgy} \ mathrm {μs}^{ - 1} $的平均剂量率，在时间窗口中，最高$ 10 \，\ mathrm {μs} $，可以在光束诱导的聚集的启动之前捕获蛋白质动力学。我们将这种方法称为聚集之前的相关性，并证明MHz-XPC桥接了生物样品测量技术中重要的时空间隙。
X-ray free-electron lasers (XFELs) with megahertz repetition rate can provide novel insights into structural dynamics of biological macromolecule solutions. However, very high dose rates can lead to beam-induced dynamics and structural changes due to radiation damage. Here, we probe the dynamics of dense antibody protein (Ig-PEG) solutions using megahertz X-ray photon correlation spectroscopy (MHz-XPCS) at the European XFEL. By varying the total dose and dose rate, we identify a regime for measuring the motion of proteins in their first coordination shell, quantify XFEL-induced effects such as driven motion, and map out the extent of agglomeration dynamics. The results indicate that for average dose rates below $1.06\,\mathrm{kGy}\mathrm{μs}^{-1}$ in a time window up to $10\,\mathrm{μs}$, it is possible to capture the protein dynamics before the onset of beam induced aggregation. We refer to this approach as correlation before aggregation and demonstrate that MHz-XPCS bridges an important spatio-temporal gap in measurement techniques for biological samples.
