A generic model for pH-sensitive collapse of hydrophobic polymers

Area of Science:

• Biophysics
• Polymer Science
• Computational Chemistry

Background:

• The hydrophobic effect is crucial for protein stability and is influenced by environmental factors like pH.
• Understanding pH effects on protein structure is vital for various biological and biotechnological applications.

Purpose of the Study:

• To develop a simplified model system to investigate the influence of pH on the hydrophobic effect in polymers.
• To explore how titratable monomers affect polymer conformation and stability at different pH values.

Main Methods:

• Parameterization of biologically motivated titratable monomers.
• Constant pH molecular dynamics (MD) simulations of polymers with inserted titratable monomers.
• Calculation of the potential of mean force as a function of polymer radius of gyration.

Main Results:

• Polymer collapse is destabilized by increased monomer charge (high pH for acidic, low pH for basic monomers).
• Monomer position within the polymer sequence influences the degree of destabilization.
• Monomer pKa values are sensitive to polymer conformation, mirroring protein behavior.
• A zwitterionic polymer exhibited pH-dependent hairpin formation.

Conclusions:

• The model provides a powerful framework for studying pH effects on hydrophobic interactions.
• Findings offer insights into intrinsically disordered proteins (IDPs) and pH-responsive drug delivery systems.