Theoretical Sum Frequency Generation Spectroscopy of Peptides

Area of Science:

• Biophysical Chemistry
• Spectroscopy
• Computational Biology

Background:

• Vibrational sum frequency generation (SFG) spectroscopy is a powerful tool for studying molecular structures at interfaces.
• Chiral SFG techniques are particularly sensitive to protein secondary structures, offering enhanced discrimination.
• Previous applications include antimicrobial peptides, ion channels, and amyloid polypeptides.

Purpose of the Study:

• To develop a theoretical strategy for calculating protein amide I SFG spectra.
• To demonstrate the utility of chiral SFG for analyzing peptide secondary structure and orientation.
• To provide a framework for interpreting experimental SFG data.

Main Methods:

• Combining line-shape theory with molecular dynamics simulations to model protein SFG spectra.
• Applying the theoretical approach to three model peptides.
• Analyzing the dependence of SFG signals on peptide orientation, dynamics, and coupling effects.

Main Results:

• Demonstrated a significant chiral SFG signal in peptides with chiral centers.
• Established a framework for interpreting SFG spectra based on peptide orientation.
• Investigated the influence of dynamical and coupling effects on SFG signals.
• Proposed and tested a method for determining chromophore orientation using heterodyne-detected SFG signals.

Conclusions:

• Chiral SFG spectroscopy, supported by theoretical calculations, is a valuable method for characterizing protein secondary structure and orientation at interfaces.
• The developed theoretical strategy provides insights into spectral interpretation and aids in experimental design.
• A simple method for determining chromophore orientation from experimental data was validated.