Pan Zhijun, Huang Jing, Zhuang Wei
State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 35000, China.
Shenzhen Bay Laboratory, Guangming District, Shenzhen 518107, China.
JACS Au. 2021 Sep 15;1(10):1788-1797. doi: 10.1021/jacsau.1c00356. eCollection 2021 Oct 25.
Picosecond fast motions and their involvement in the biochemical processes such as protein-ligand binding has engaged significant attention. Terahertz optical Kerr spectroscopy (OKE) has the superior potential to probe these fast motions directly. Application of OKE in protein-ligand binding study is, however, limited by the difficulty of quantitative atomistic interpretation, and the calculation of Kerr spectrum for entire solvated protein complex was considered not yet feasible, due to the lack of one consistent polarizable model for both configuration sampling and polarizability calculation. Here, we analyzed the biochemical relevance of OKE to the lysozyme-triacetylchitotriose binding based on the first OKE simulation using one consistent Drude polarizable model. An analytical multipole and induced dipole scheme was employed to calculate the off-diagonal Drude polarizability more efficiently and accurately. Further theoretical analysis revealed how the subtle twisting and stiffening of aromatic protein residues' spatial arrangement as well as the confinement of small water clusters between ligand and protein cavity due to the ligand binding can be examined using Kerr spectroscopy. Comparison between the signals of bound complex and that of uncorrelated protein/ligand demonstrated that binding action alone has reflection in the OKE spectrum. Our study indicated OKE as a powerful terahertz probe for protein-ligand binding chemistry and dynamics.
皮秒级快速运动及其在诸如蛋白质 - 配体结合等生化过程中的作用已引起了广泛关注。太赫兹光克尔光谱（OKE）具有直接探测这些快速运动的卓越潜力。然而，OKE在蛋白质 - 配体结合研究中的应用受到定量原子解释困难的限制，并且由于缺乏一种适用于构型采样和极化率计算的一致可极化模型，计算整个溶剂化蛋白质复合物的克尔光谱被认为尚不可行。在此，我们基于首次使用一致的德鲁德可极化模型进行的OKE模拟，分析了OKE与溶菌酶 - 三乙酰壳三糖结合的生化相关性。采用了一种解析多极和诱导偶极方案，更高效、准确地计算非对角德鲁德极化率。进一步的理论分析揭示了如何利用克尔光谱研究芳香族蛋白质残基空间排列的细微扭曲和变硬，以及由于配体结合导致配体与蛋白质腔之间小水团簇的限制。结合复合物与不相关蛋白质/配体信号之间的比较表明，仅结合作用就反映在OKE光谱中。我们的研究表明OKE是用于蛋白质 - 配体结合化学和动力学的强大太赫兹探针。
