Discriminating trpzip2 and trpzip4 peptides' folding landscape using the two-dimensional infrared spectroscopy: a...

Area of Science:

• Biophysics
• Computational Chemistry
• Spectroscopy

Background:

• Understanding peptide folding is crucial for protein science.
• β-hairpin peptides like trpzip2 and trpzip4 serve as model systems.
• Distinguishing folding landscapes of similar peptides is challenging.

Purpose of the Study:

• To analyze how differences in folding landscapes of trpzip2 and trpzip4 peptides manifest in thermal unfolding.
• To investigate the sensitivity of infrared (IR) spectral features to local thermal stability variations.

Main Methods:

• Theoretical spectroscopic modeling using nonlinear exciton propagation.
• Calculation of isotope-edited equilibrium Fourier-transform infrared (FTIR) and 2D IR spectra.
• Molecular dynamics (MD) simulations with GB(OBC) implicit solvent and integrated tempering sampling.

Main Results:

• Conformational analysis revealed differing local thermal stabilities between trpzip2 and trpzip4.
• These stability differences correlate with distinct peptide folding landscapes.
• Ellipticities of isotope peaks in coherent IR signals showed higher sensitivity to local stability differences than peak intensities.

Conclusions:

• The study provides a theoretical framework to interpret experimental IR measurements of peptide thermal unfolding.
• The findings suggest that IR spectroscopy, particularly isotope peak ellipticities, can effectively probe subtle differences in peptide folding landscapes.
• This approach enhances understanding of peptide folding dynamics and stability.