Li Jinyu, Lyu Wenping, Rossetti Giulia, Konijnenberg Albert, Natalello Antonino, Ippoliti Emiliano, Orozco Modesto, Sobott Frank, Grandori Rita, Carloni Paolo
College of Chemistry, Fuzhou University , 350002 Fuzhou, China.
Computational Biomedicine, Institute for Advanced Simulation IAS-5 and Institute of Neuroscience and Medicine INM-9, Forschungszentrum Jülich , 52425 Jülich, Germany.
J Phys Chem Lett. 2017 Mar 16;8(6):1105-1112. doi: 10.1021/acs.jpclett.7b00127. Epub 2017 Feb 22.
Native electrospray ionization/ion mobility-mass spectrometry (ESI/IM-MS) allows an accurate determination of low-resolution structural features of proteins. Yet, the presence of proton dynamics, observed already by us for DNA in the gas phase, and its impact on protein structural determinants, have not been investigated so far. Here, we address this issue by a multistep simulation strategy on a pharmacologically relevant peptide, the N-terminal residues of amyloid-β peptide (Aβ(1-16)). Our calculations reproduce the experimental maximum charge state from ESI-MS and are also in fair agreement with collision cross section (CCS) data measured here by ESI/IM-MS. Although the main structural features are preserved, subtle conformational changes do take place in the first ∼0.1 ms of dynamics. In addition, intramolecular proton dynamics processes occur on the picosecond-time scale in the gas phase as emerging from quantum mechanics/molecular mechanics (QM/MM) simulations at the B3LYP level of theory. We conclude that proton transfer phenomena do occur frequently during fly time in ESI-MS experiments (typically on the millisecond time scale). However, the structural changes associated with the process do not significantly affect the structural determinants.
原生电喷雾电离/离子淌度-质谱（ESI/IM-MS）能够精确测定蛋白质的低分辨率结构特征。然而，我们在气相中对DNA早已观察到的质子动力学现象及其对蛋白质结构决定因素的影响，迄今尚未得到研究。在此，我们通过对一种具有药理相关性的肽——淀粉样β肽（Aβ(1-16)）的N端残基采用多步模拟策略来解决这一问题。我们的计算重现了ESI-MS实验中的最大电荷态，并且与这里通过ESI/IM-MS测量的碰撞截面（CCS）数据也相当吻合。尽管主要结构特征得以保留，但在动力学的最初约0.1毫秒内确实发生了细微的构象变化。此外，从理论B3LYP水平的量子力学/分子力学（QM/MM）模拟中可以看出，气相中分子内质子动力学过程发生在皮秒时间尺度上。我们得出结论，在ESI-MS实验的飞行时间内（通常在毫秒时间尺度上）质子转移现象确实频繁发生。然而，与该过程相关的结构变化并未显著影响结构决定因素。
