Unusual Hydrations of Amide I: An Insight into Protein Structure and Flexibility

Area of Science:

• Biochemistry
• Physical Chemistry
• Computational Chemistry

Background:

• Deuterium's higher atomic mass impacts hydrogen bonding and solvation.
• This raises concerns about the accuracy of biomolecular measurements in heavy water (D2O).

Purpose of the Study:

• To investigate how solvent isotopic exchange affects protein structure and dynamics.
• To compare biomolecular behavior in protonated versus deuterated solvents.

Main Methods:

• Linear infrared (IR) spectroscopy
• Circular dichroism (CD) spectroscopy
• Molecular dynamics (MD) simulations
• Density functional theory (DFT) calculations

Main Results:

• Deuterated solvents (D2O, CD3OD) exhibit longer hydrogen-bond lifetimes compared to protonated solvents (H2O, CH3OH).
• Slower hydrogen-bond dynamics and reduced protein backbone flexibility were observed in deuterated solvents.
• Differences in solvation patterns and protein secondary structure stability were noted.

Conclusions:

• Biomolecular structures and dynamics differ significantly between deuterated and protonated solvents.
• Isotope substitution effects are intrinsic and not unique to water.
• Experimental data in D2O requires careful interpretation for native biological conditions.