Two-Dimensional Infrared (2DIR) Spectroscopy of the Peptide Beta3s Folding

Probing the underlying free-energy landscape, pathway, and mechanism is the key to understanding protein folding in theory and experiment. Time-resolved two-dimensional infrared (2DIR) with femtosecond laser pulses has emerged as a powerful tool for investigating the protein folding dynamics on much faster time scales than possible by NMR. We have employed molecular dynamics simulations to compute 2DIR spectra of the folding process of a peptide, Beta3s. Simulated nonchiral and chiral 2DIR signals illustrate the variation of the spectra as the peptide conformation evolves along the free-energy landscape. Chiral spectra show stronger changes than the nonchiral signals because cross peaks caused by the formation of the β-sheet are clearly resolved. Chirality-induced 2DIR may be used to detect the folding of β-sheet proteins with high spectral and temporal resolution.