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

Abstract

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.