Charge Regulation Dramatically Enhances Weak Polyelectrolyte Complexation

We use coarse-grained simulations to study the impact of charge regulation on the complexation of a weak polyacid and a strong polycation. Comparing an isolated polyacid with the polyelectrolyte pair, we demonstrate that charge regulation leads to a significant enhancement of the ionization, amounting to an overall pKA shift of more than three units. Furthermore, our simulations unveil that the condensation of isolated chains into a tightly bound complex happens in a discontinous, first-order like transition as the pH value is varied. These results are corroborated using enhanced sampling calculations, which reveal the presence of a free energy barrier at the transition pH. To quantify the observed charge regulation effects, we compare binding constants of the complex, calculated under charge regulating and constant charge conditions. We find that charge regulation dramatically enhances the binding affinity of the complex, emphasizing the importance of including fluctuating charges in a theoretical description.