Salt Bridge in Aqueous Solution: Strong Structural Motifs but Weak Enthalpic Effect

Area of Science:

• Protein structure and stability
• Biophysical chemistry
• Computational biology

Background:

• Salt bridges are crucial for protein secondary and tertiary structure, contributing to stability.
• These motifs are often solvent-exposed and interact with water and cosolvents, including ions.

Purpose of the Study:

• To investigate the influence of simple salt ions on an Arginine-Aspartic acid salt bridge in aqueous solution.
• To understand the specific interactions and effects of ions on salt bridge dynamics and stability.

Main Methods:

• Molecular dynamics simulations were employed to study the Arginine-Aspartic acid salt bridge.
• Mean force calculations along the salt bridge dissociation pathway were performed.

Main Results:

• Solvated ions, specifically Li+ and Na+, were observed to form tight ionic pairs with Aspartic acid residues.
• These ions influenced the salt bridge behavior in a specific and local manner.
• The enthalpic contribution of the salt bridge to protein stability was found to be minor, even with ion presence.

Conclusions:

• Solvated ions can locally modulate protein salt bridge interactions.
• The formation of ion-Aspartate pairs is a key interaction mechanism.
• The overall enthalpic contribution of salt bridges to protein stability may be less significant than previously assumed.