The overall TCF, C O (τ ), was determined by calculating the rotation matrix between the reference structure of the protein and the structure of the protein at every time frame from the MD simulation. By using the rotation matrix, the quaternion representation was calculated and hence the elements of the diffusion tensor. The TCFs were calculated based on the ten 100 ns trajectories. The trajectories were grouped into 5 chunks. The TCFs were calculated for each chunk and then averaged. Each averaged TCF was fitted up to a lag time of 10 ns to yield C O (τ ). Diffusion constants for each chunk were averaged and the standard deviation of the 5 chunks was used to estimate the statistical uncertainty.