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.