Anharmonic Vibrational Analyses of Pentapeptide Conformations Explored with Enhanced Sampling Simulations

Area of Science:

• Computational Chemistry
• Spectroscopy
• Biophysics

Background:

• Accurate theoretical prediction of polypeptide vibrational spectra is difficult due to conformational flexibility and anharmonic effects.
• Existing methods require expensive quantum mechanical calculations for both electrons and vibrations.
• Identifying relevant conformers contributing to the spectrum is a significant challenge.

Purpose of the Study:

• To develop a novel theoretical approach for accurate vibrational spectrum prediction of polypeptides.
• To address the challenges posed by conformational flexibility and anharmonic effects in spectral analysis.
• To reduce the computational cost associated with vibrational structure calculations.

Main Methods:

• Enhanced conformational sampling using replica-exchange molecular dynamics.
• Structural clustering to identify distinct peptide conformations.
• Vibrational structure calculation using second-order vibrational quasi-degenerate perturbation theory (VQDPT2).
• Systematic mode-selection scheme to reduce VQDPT2 computational cost.

Main Results:

• The proposed method accurately predicted the infrared spectrum of a pentapeptide (SIVSF-NH2) in the OH and NH stretching region.
• The theoretical spectrum of the lowest energy conformer showed a mean absolute deviation of 11.2 cm-1 from the experimental spectrum.
• NH stretching frequencies of the five lowest energy conformers aligned with literature values for similar small peptides.

Conclusions:

• The developed theoretical approach is a promising tool for analyzing polypeptide vibrational spectra.
• The method effectively balances accuracy and computational cost for complex biomolecules.
• This work advances the capability to theoretically study peptide dynamics and structure through vibrational spectroscopy.