Study of Correlated Motions to Detect the Conformational Transitions of the Intrinsically Disordered Sheep Prion Peptide

Intrinsically disordered proteins (IDPs) are known for
their random
structural changes throughout their sequence based on the environment.
The mechanism underlying these structural changes is difficult to
explain. All biological processes are known to follow the direction
through which they act. A study of the correlated motion can help
to understand the direction of the change. Herein, we introduced the
multivariate statistical analysis (MSA) technique to study the correlated
motion of the peptide. The correlated motion of the sheep prion peptide
was studied with the change in the temperature and solvent. These
techniques helped to identify the contributing residual motions that
helped to form the different secondary structures of the protein and
also the triggering factors that drive these sorts of residual motions.
The structural details match the experimentally reported data. It
was found that the direction of the change of the secondary structure
for this peptide shifted from the C-terminal to the N-terminal with
an increase in the temperature. It was found that the involvement
of the hydrophobic residues present at the C-terminal and the middle
residues (residues 12–17) is responsible for forming a β-sheet
at the normal temperature. Hydration water was found to play an important
role in this change. Insights gained from this study can be used to
design strategies for desirable structural changes in the IDPs.