Site-Specific Vibrational Dynamics to Probe Local and Global Protein Motions

Abstract

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.