Normal mode paths for hydrogen exchange in the peptide ferrichrome

Area of Science:

• Biochemistry
• Computational Chemistry
• Molecular Dynamics

Background:

• Ferrichrome is a cyclic hexapeptide with potential for solvent exposure and hydrogen exchange.
• Amide proton exchange in peptides is crucial for understanding their structure and function.
• Previous studies have not fully elucidated the dynamic pathways for solvent accessibility in ferrichrome.

Purpose of the Study:

• To investigate the dynamic pathways for solvent exposure and hydrogen exchange of amide protons in ferrichrome.
• To identify specific molecular motions that facilitate the accessibility of buried exchangeable groups.
• To correlate these motions with changes in hydrogen bonding and conformational flexibility.

Main Methods:

• Vibrational normal mode calculations were performed on the ferrichrome molecule.
• The solvent accessible surface area (SASA) algorithm was employed to quantify exposure.
• Analysis focused on low-energy atomic displacements and correlated dihedral angle changes.

Main Results:

• Glycine amide protons (Gly(1,2,3,)) are largely solvent-exposed in the crystal structure.
• Ornithine amide protons (Orn(1,2,3,)) are initially shielded from solvent.
• Low-frequency vibrational modes (approx. 18 cm(-1)) were found to expose Orn(2) and Orn(3) amide groups, while Orn(1) remained shielded.

Conclusions:

• Specific low-frequency vibrational motions dictate the solvent accessibility of ferrichrome's amide protons.
• These dynamic pathways are critical for understanding hydrogen exchange mechanisms in cyclic peptides.
• The findings provide insights into the conformational flexibility and solvent interactions of ferrichrome.