Energetics of cosolvent effect on peptide aggregation

Area of Science:

• Biophysical Chemistry
• Chemical Thermodynamics
• Molecular Modeling

Background:

• Peptide aggregation is a critical process in biological systems and disease.
• Understanding the influence of cosolvents on peptide aggregation is essential for therapeutic development.
• Energetic perspectives offer a fundamental approach to studying chemical equilibria.

Purpose of the Study:

• To review the cosolvent effect on peptide aggregation equilibrium from an energetic viewpoint.
• To elucidate the relationship between excess chemical potential, solute configuration, and solvation free energy.
• To analyze the impact of specific cosolvents (urea, DMSO) on peptide aggregation using computational methods.

Main Methods:

• Theoretical review of cosolvent effects on chemical equilibrium.
• Application of the energy-representation method to compute solvation free energy.
• All-atom molecular modeling simulations for an 11-residue peptide.

Main Results:

• Excess chemical potential is stationary against solute configuration variations.
• Cosolvent concentration effects are linked to solvation free energy differences.
• Urea and DMSO enhance solvation, inhibiting aggregation, with diminishing effect on larger aggregates.

Conclusions:

• Cosolvents like urea and DMSO act as inhibitors of peptide aggregation.
• The degree of inhibition is dependent on aggregate size and specific intermolecular interactions.
• Electrostatic, van der Waals, and excluded-volume interactions play key roles in cosolvent effects.