Dynamic Water-Mediated Hydrogen Bonding in a Collagen Model Peptide

Area of Science:

• Biochemistry
• Structural Biology
• Biophysics

Background:

• The fibrillar collagen triple helix relies on direct interchain hydrogen bonding for stability.
• Glycine mutations in collagen disrupt these bonds and are linked to connective tissue diseases.

Purpose of the Study:

• To investigate the dynamic hydrogen bonding in collagen peptides with glycine substitutions.
• To compare solution conformation and dynamics with existing X-ray crystal structures.

Main Methods:

• Integration of computational approaches (Molecular Dynamics simulations) with Nuclear Magnetic Resonance (NMR).
• Theoretical calculations of NMR chemical shifts using quantum fragmentation.
• Analysis of peptide conformation, dynamics, and hydrogen bonding patterns.

Main Results:

• Solution conformation and hydrogen bonding differ significantly from X-ray crystal structures.
• Evidence of inequivalent environments in the three collagen chains.
• Identified distinct hydrogen bonding patterns (direct, water bridges, nonbridging waters) at glycine substitution sites.

Conclusions:

• NMR and MD data reveal the dynamic nature of collagen hydrogen bonding.
• Amide shifts are sensitive to acceptor groups, including water.
• Provides insights into collagen structure, dynamics, and receptor recognition, aiding interpretation of glycine substitutions and sequence interruptions.