Simple model of pH-induced protein denaturation

Area of Science:

• Protein folding and denaturation
• Computational biophysics
• Statistical mechanics

Background:

• Protein structure is highly sensitive to pH.
• Conventional hydrophobic-polar (HP) models do not fully capture pH-induced effects.
• Electrostatic interactions are key drivers of pH-induced protein unfolding.

Purpose of the Study:

• To systematically study pH-induced protein conformational changes.
• To develop a simplified model incorporating electrostatic interactions.
• To investigate the transition from native to denatured states.

Main Methods:

• Utilizing a lattice-based hydrophobic-polar (HP) model.
• Incorporating electrostatic repulsion between polar (P) monomers.
• Exact enumeration of protein chains (14- to 18-mers).

Main Results:

• Lowest-energy states shift from single native to multiple denatured conformations with increased electrostatic repulsion.
• Conformational state switching resembles real proteins, typically between two states.
• Denatured states exhibit broad structural fluctuations, akin to molten globule states.

Conclusions:

• The proposed HP model with electrostatic interactions provides a simplified physical picture of pH-induced protein denaturation.
• The model accurately predicts the transition to multiple denatured states.
• Structural fluctuations in denatured states are consistent with experimental observations of molten globules.