Amide I IR, VCD, and 2D IR Spectra of Isotope-labeled α-helix in liquid water: Numerical simulation studies

Amide I infrared (IR), vibrational circular dichroism (VCD), and two-dimensional IR (2D IR) spectra of various isotope-labeled α-helical polyalanines in liquid water were theoretically calculated by combining semiempirical quantum chemistry calculation, Hessian matrix reconstruction, fragmentation approximation, and molecular dynamics simulation methods. The solvation-induced amide I frequency shift was found to be about -20 cm ^-1. Properly taking into account the motional narrowing effect in the ensemble averaging, we show that the simulated IR, VCD, and 2D IR spectra are quantitatively in good agreement with experimental results. Depending on the relative positions of the ¹³C and/or ¹³C=¹⁸O labeled peptides in a given α-helix, the IR absorption line shape, IR intensity distribution, positive-negative VCD pattern, and diagonal/off-diagonal 2D IR echo spectral features were found to change dramatically. It is shown that these different spectroscopic observations can be described in a consistent manner by using the present simulation method. We will show that the properly designed isotopomers and their IR, VCD, and 2D IR spectrum analyses can provide incisive information on the three-dimensional polypeptide structure and dynamics.