Assignment of Protein Collective Structural Vibrations Steering Conformational Change

Collective vibrations from elastic network models (ENM) have been used to predict protein intermediate state structures.  The underlying assumption is that these vibrational displacements provide a trajectory towards the intermediate state conformation.  In reality structural vibrations have small displacement amplitudes, insufficient to reach the intermediate state.  Further ENM vibrations do not capture the complexity and variability of an all atom system which samples multiple configurations.  Despite this variability, measurements of the anisotropic terahertz absorption find spectral structure for macroscopic protein samples indicating specific displacement directions concentrated in specific energy bands emerge from this complexity.  This suggests that while no single vibration is responsible for a conformational transition, the overall dynamics of the system is biased towards the intermediate state displacements.  Here we present strategies to assign the spectrally observed bands with structural displacements based on normal mode ensemble analysis (NMEA).  A projection analysis on a full ensemble of vibrations of lysozyme using a vibrational displacement basis set from ENM shows narrow frequency ranges are dominated by specific displacements. As a second strategy, we examine correlations in structural displacements for resonant bands in the calculated anisotropic absorbance for the photo protective protein, orange carotenoid protein.