Amide Nitrogen Pyramidalization via N-H/N Interactions that Stabilize the δ/α Conformations in Turns, Loops, and 3₁₀-...

Area of Science:

• Protein structure and dynamics
• Molecular interactions
• Biochemistry

Background:

• N-H/N interactions are observed in protein structures like turns, loops, and helices.
• Their precise role in protein structure and dynamics is not fully understood.

Purpose of the Study:

• To investigate the inherent nature of N-H/N interactions.
• To understand their impact on protein structure and dynamics.

Main Methods:

• Obtained crystal structure of a molecule with an N-H/N interaction.
• Performed DFT calculations on model compounds.
• Analyzed small-molecule crystal structures.
• Examined PDB for N-H/N interactions across canonical amino acids.

Main Results:

• Observed a close H···N distance (2.30 Å) and significant nitrogen pyramidalization (12°) in a crystal structure.
• DFT calculations confirmed nitrogen pyramidalization and reduced amide planarity are inherent to N-H/N interactions.
• N-H/N interactions lower the energy barrier for proline cis-trans isomerization.

Conclusions:

• N-H/N interactions are intrinsic structural elements in proteins.
• They influence protein folding pathways and stability.
• These interactions are prevalent across all 20 canonical amino acids in specific conformations.