Orientation affects hydrogen bonding cooperativity in polyproline II helical bundles

Area of Science:

• Biophysics
• Structural Biology
• Computational Chemistry

Background:

• Hydrogen bond cooperativity (HBC) enhances hydrogen bond networks, crucial for protein stability, particularly in α-helices and β-sheets.
• Polyproline II (PPII) helices are increasingly recognized in natural proteins, but HBC in their antiparallel or mixed assemblies remains uncharacterized.

Purpose of the Study:

• To investigate the existence and nature of hydrogen bond cooperativity in antiparallel and mixed parallel/antiparallel polyproline II helix assemblies.
• To elucidate the hydrogen bonding schemes governing HBC in these PPII helix configurations.

Main Methods:

• Employed computational approaches to model and analyze hydrogen bonding interactions.
• Validated computational findings using experimental observables to ensure accuracy.

Main Results:

• Demonstrated that both canonical CO···HN and non-canonical CO···HαCα hydrogen bonds exhibit mutual reinforcement in antiparallel and mixed PPII helices.
• Revealed a complex hydrogen bonding network that manifests HBC in these PPII helix arrangements.

Conclusions:

• Hydrogen bond cooperativity is present in antiparallel and mixed PPII helix assemblies, not just parallel ones.
• These findings are vital for understanding protein conformational stability and the role of PPII helices in protein design.