Figure 3: Projection of the first two principal components of the five simulated systems. Unmodified Tau (Tau_plane) showing wide distribution of conformational sampling, while Tau_glyc & Tau_phos occupies a more concentrated conformational space. Tau_p356 and Tau_p352 show the most widespread distribution of conformational space.
Large conformational changes in the protein cause the spreading of the distribution in the conformational space. Figure 3 suggest that the conformational space occupied by Tau_plane is widely distributed indicating the wide range of conformational states occupied by the protein over the course of the entire trajectory, while Tau_glyc is having a relatively narrow conformational space as compared to Tau_plane. Tau_phos have the most concentrated conformational sampling, suggesting a stable conformational space occupied the phosphorylated system. Tau_p356 and Tau_p352 show concentrated conformational groupings, which are separated from each other, suggesting clustering of conformations.
In order to get deeper insights into the essential motions of tau in each of the systems, we extracted the movements of the protein across the first and second principal components. The functionally relevant motions of each of the tau systems as represented by the first two principal components are given in the supporting information (Movie S1 ) as movies . It is evident from the motions that unmodified tau (Tau_plane) tend to exist in an extended conformation as we can observe the motions suggest the peptide chain is forming elongated conformation. But this is not the case with N-glycosylated system, as we can see that the glycan is inducing the peptide system to fold. The phosphorylated system (Tau_phos) also follows a similar trend as we can see the peptide getting folded, rather than extending. Tau_p356 and Tau_p352 both do not show much folding tendency as the fundamental motions suggest they exist in an elongated form.
Results of the analysis of essential dynamics of the protein systems are in line with the previous analysis given above, suggesting that the glycosylated (Tau_glyc) and phosphorylated (Tau_phos) systems are actually folding and largely exist in a folded state whereas unmodified tau is largely existing in an open extended state.