Computational spectroscopy of ubiquitin: comparison between theory and experiments

Area of Science:

• Computational chemistry
• Biophysics
• Spectroscopy

Background:

• Proteins exhibit complex vibrational spectra.
• Accurate simulation of these spectra is essential for understanding protein structure and dynamics.
• Existing computational methods face challenges in quantitatively predicting certain spectral features.

Purpose of the Study:

• To establish computational schemes for simulating amide I IR absorption, vibrational circular dichroism (VCD), and 2D IR photon echo spectra of ubiquitin in water.
• To investigate the vibrational characteristic features in the amide I vibration region.
• To assess the quantitative validity of the developed computational methods by comparing simulated spectra with experimental data.

Main Methods:

• Constrained molecular dynamics simulations
• Quantum chemistry calculations (semiempirical)
• Hessian matrix reconstruction
• Fragmentation approximation methods

Main Results:

• Amide I local mode frequencies and vibrational coupling constants for ubiquitin were determined.
• High heterogeneity and site dependency of amide I local mode frequencies were observed in both gas and aqueous phases.
• Simulated amide I IR and 2D IR spectra showed good agreement with experimental data.
• Simulated VCD spectrum showed only qualitative agreement, highlighting sensitivity to local mode frequency accuracy.

Conclusions:

• The site dependency of amide I local mode frequencies (diagonal heterogeneity) is critical for accurate protein VCD spectrum prediction.
• The developed computational methods are valuable for refining classical force fields.
• These methods will aid in understanding protein structure-spectra relationships in solution.