Solvation stabilizes intercarbonyl n→π* interactions and polyproline II helix

Area of Science:

• Computational Chemistry
• Biophysics
• Protein Structure

Background:

• n→π* interactions between carbonyl groups are crucial for protein secondary structures like alpha-helix and polyproline II helix (PPII).
• These interactions are thought to influence the conformational preferences of disordered protein states.

Purpose of the Study:

• To investigate the impact of explicit solvation on the strength of n→π* interactions.
• To understand how different solvent molecules and ions affect these interactions in model systems and peptides.

Main Methods:

• Computational investigations of a model n→π* interaction (formaldehyde dimer) with explicit solvation (water, HF).
• Examination of effects of urea, thiourea, guanidinium, and monovalent cations.
• Analysis of solvent effects in model peptides (Ac-Pro-NMe2, Ac-Ala-NMe2, Ac-Pro2-NMe2).

Main Results:

• Solvation of the acceptor carbonyl significantly enhances n→π* interaction strength; donor carbonyl solvation has a modest weakening effect.
• Maximum interaction strength observed with two solvent molecules on the acceptor carbonyl.
• In peptides, acceptor carbonyl solvation leads to more compact conformations, reduces energy differences between proline ring puckers, and favors PPII over alpha-helix and beta-conformations.

Conclusions:

• Explicit solvation plays a critical role in modulating n→π* interaction strength.
• Carbonyl solvation energetically favors the polyproline II helix conformation, aligning with experimental observations in protic solvents and denaturants.
• Solvation effects on n→π* interactions provide insights into protein conformational preferences in solution.