用于探测蛋白质局部与整体运动的位点特异性振动动力学
Site-Specific Vibrational Dynamics to Probe Local and Global Protein Motions
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中文总结 AI 辅助
本研究以溶菌酶的--SCN、--N₃等标记物为对象，用机器学习模型结合频率涨落关联函数，证实位点特异性振动探针可探测蛋白质局部及集体运动，为相关研究提供了定性验证。
中文摘要 AI 辅助
振动光谱探针可提供蛋白质结构与动力学的位点特异性信息。本研究探究了将蛋白质运动与共价连接在溶菌酶所有丙氨酸残基上的--SCN、--N₃和--SNO标记物的振动响应相关联的可能性。根据探针沿多肽链的位置、其局部水合状态及周围环境的动力学，振动响应不仅可编码局部涨落，还可编码蛋白质的低频集体运动。采用基于机器学习的模型描述光谱探针：键合相互作用用再生核模型表示，静电相互作用用波动型最小分布电荷表示。光谱动力学通过频率涨落关联函数（FFCFs）表征。对于多数探针位置，FFCFs在模拟时间尺度上包含不衰减分量，表明存在残余慢动力学及潜在构象涨落的不完全采样。这些静态贡献的幅度与先前实验观察结果一致，为模拟提供了定性验证。总体而言，结果表明位点特异性振动探针可报告超出其紧邻局部环境的动力学，且在合适位置可提供蛋白质集体运动的信息。
英文摘要
Vibrational spectroscopic probes can provide site-specific information on protein structure and dynamics. In this work, the possibility to relate protein motion with the vibrational response for --SCN, --N$_3$, and --SNO labels covalently linked to all alanine-residues in lysozyme is investigated. Depending on the position of the probe along the polypeptide chain, its local hydration, and the dynamics of its environment, the vibrational response can encode not only local fluctuations but also low-frequency, collective motions of the protein. The spectroscopic probes are described using machine-learning-based models for both bonded interactions, represented by reproducing-kernel models, and electrostatic interactions, represented by fluctuating minimally distributed charges. Spectroscopic dynamics are characterized through frequency fluctuation correlation functions (FFCFs). For many probe locations, the FFCFs contain a non-decaying component on the simulation time scale, indicating residual slow dynamics and incomplete sampling of the underlying conformational fluctuations. The magnitude of these static contributions is consistent with previous experimental observations, providing qualitative validation of the simulations. Overall, the results demonstrate that site-specific vibrational probes can report on dynamics extending beyond their immediate local environment and can, at suitable locations, provide information on collective protein motions.
