Lehrstuhl für BioMolekulare Optik, Ludwig-Maximilians-Universität, 80538, Munich, Germany.
Sci Rep. 2021 Jul 2;11(1):13774. doi: 10.1038/s41598-021-93326-1.
In this investigation, we report the effect on the microscopic dynamics and interactions of the cytokine interferon gamma (IFN-γ) and antibodies to IFN-γ (anti-IFN-γ) and to the interferon gamma receptor 1 (anti-IFNGR1) prepared in exceptionally dilute solutions of initial proteins. Using both THz spectroscopy and molecular dynamics simulations we have uncovered that the high dilution method of sample preparation results in the reorganization of the sample surface residue dynamics at the solvent-protein interface that leads to both structural and kinetic heterogeneous dynamics that ultimately create interactions that enhance the binding probability of the antigen binding site. Our results indicate that the modified interfacial dynamics of anti-IFN-γ and anti-IFGNR1 that we probe experimentally are directly associated with alterations in the complementarity regions of the distinct antibodies that designate both antigen-antibody affinity and recognition.
在这项研究中，我们报告了细胞因子干扰素γ（IFN-γ）和针对 IFN-γ（抗 IFN-γ）以及干扰素γ受体 1（抗 IFNGR1）的抗体在初始蛋白质异常稀释溶液中的微观动力学和相互作用的影响。使用太赫兹光谱和分子动力学模拟，我们发现，样品制备的高稀释方法导致了样品表面残基在溶剂-蛋白质界面处的动力学重新组织，从而导致结构和动力学的不均匀性，最终产生增强抗原结合位点结合概率的相互作用。我们的结果表明，我们实验探测到的抗 IFN-γ和抗 IFNGR1 的界面动力学的改变与不同抗体的互补区域的改变直接相关，这些改变决定了抗原-抗体的亲和力和识别。
