Adhesive-cohesive model for protein compressibility: an alternative perspective on stability

Area of Science:

• Protein dynamics and structural biology
• Biophysics and computational biology

Background:

• Protein compressibility is a dynamic property reflecting forces governing structural stability.
• Understanding variations in compressibility among globular proteins is crucial for deciphering protein folding and stability.

Purpose of the Study:

• To establish a link between intrinsic protein compressibility and protein stability.
• To identify the molecular basis for variations in compressibility across different globular proteins.
• To develop a model explaining the relationship between charge distribution and protein compressibility.

Main Methods:

• Utilized molecular dynamics simulations to analyze protein compressibility.
• Investigated a larger dataset of globular proteins to validate findings.
• Developed an adhesive-cohesive model based on charge distribution and solvent interactions.

Main Results:

• Excess surface charge was identified as the primary factor explaining variations in protein compressibility.
• An adhesive-cohesive model was proposed, highlighting the interplay between solvent attraction and tertiary interactions.
• A correlation between compressibility and heat capacity of unfolding suggests a link to enthalpy of unfolding.

Conclusions:

• Folded proteins can achieve greater enthalpic stability through uniform distribution of charged atoms, rather than surface partitioning.
• Internal positioning of charged groups, in optimal structural arrangements, may contribute to protein stability.
• The findings address the fundamental question of whether buried charged groups can be energetically stabilizing.