Center for Life Nano & Neuro Science, Istituto Italiano di Tecnologia, Viale Regina Elena 291, 00161 Rome, Italy.
Department of Physics, Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, Italy.
J Phys Chem Lett. 2024 Apr 4;15(13):3478-3485. doi: 10.1021/acs.jpclett.3c03632. Epub 2024 Mar 21.
We propose a novel approach for detecting the binding between proteins making use of the anomalous diffraction of natively present heavy elements, e.g., sulfurs, inside molecular three-dimensional structures. In particular, we analytically and numerically show that the diffraction patterns produced by the anomalous scattering of the sulfur atoms in a given direction depend additively on the relative distances between all couples of sulfur atoms. Thus, the differences in the patterns produced by bound proteins with respect to their nonbonded states can be exploited to rapidly assess protein complex formation. On the basis of our results, we suggest a possible experimental procedure for detecting protein-protein binding. Overall, the completely label-free and rapid method we propose may be readily extended to probe interactions on a large scale, thus paving the way for the development of a novel field of research based on a synchrotron light source.
我们提出了一种新的方法，利用天然存在的重元素（例如硫）在分子三维结构中的异常衍射来检测蛋白质之间的结合。具体来说，我们从理论和数值两方面证明了在给定方向上由硫原子的异常散射产生的衍射图案是所有硫原子对之间相对距离的加和函数。因此，结合蛋白相对于非键合状态所产生的图案差异可以用来快速评估蛋白质复合物的形成。基于我们的结果，我们提出了一种可能的实验方案来检测蛋白质-蛋白质的结合。总的来说，我们提出的这种完全无标记且快速的方法可以很容易地扩展到大规模的相互作用探测，从而为基于同步辐射光源的新研究领域的发展铺平道路。
