Gas-phase salt bridge interactions between glutamic acid and arginine

Area of Science:

• Physical Chemistry
• Computational Chemistry
• Spectroscopy

Background:

• Investigating non-covalent interactions in peptides is crucial for understanding protein structure and function.
• The interplay between charged amino acid residues like glutamic acid (Glu) and arginine (Arg) influences peptide conformation and reactivity.
• Proton transfer mechanisms in peptides are fundamental to biochemical processes.

Purpose of the Study:

• To elucidate the gas-phase side chain-side chain (SC-SC) interactions between glutamic acid and arginine residues in neutral peptides.
• To determine the conformational preferences and identify possible intramolecular proton transfer events.
• To analyze the influence of residue spacing on these interactions using low-temperature conditions.

Main Methods:

• Conformation-specific infrared (IR) spectroscopy using the free electron laser FELIX.
• Density functional theory (DFT) calculations employing B3LYP and M05-2x functionals with the 6-311+G(d,p) basis set.
• Molecular dynamics (MD) simulations with simulated annealing for identifying low-energy peptide structures.

Main Results:

• Three distinct types of SC-SC interactions were identified: two pairwise and one bifurcated.
• Experimental and computed spectra indicated a single dominant conformation for each studied peptide (Z-Glu-Ala-Arg-NHMe, n = 0,1,3).
• Specific SC-SC and dispersion interactions were observed between the arginine side chain and the Z-cap's phenyl ring, persisting despite increased residue spacing.

Conclusions:

• The study provides detailed insights into the conformational landscape and interaction mechanisms of Glu-Arg containing peptides.
• Pairwise SC-SC interactions are energetically favored in short peptide sequences.
• The findings contribute to a deeper understanding of non-covalent interactions governing peptide structure and stability.