Both Charge-Regulation and Charge-Patch Distribution Can Drive Adsorption on the Wrong Side of the Isoelectric Point.

The mechanism of protein-polyelectrolyte complexation on the wrong side of the isoelectric point has long puzzled researchers. Two alternative explanations have been proposed in the literature: (a) the charge-patch (CP) mechanism, based on the inhomogeneous distribution of charges on the protein, and (b) the charge-regulation (CR) mechanism, based on the variable charge of weak acid and base groups, which may invert the protein charge in the presence of another highly charged object. To discern these two mechanisms, we simulated artificially constructed short peptides, containing acidic and basic residues, arranged in a blocklike or alternating sequence.

Role of p in Charge Regulation and Conformation of Various Peptide Sequences.

Peptides containing amino acids with ionisable side chains represent a typical example of weak ampholytes, that is, molecules with multiple titratable acid and base groups, which generally exhibit charge regulating properties upon changes in pH. Charged groups on an ampholyte interact electrostatically with each other, and their interaction is coupled to conformation of the (macro)molecule, resulting in a complex feedback loop. Their charge-regulating properties are primarily determined by the pKA of individual ionisable side-chains, modulated by electrostatic interactions between the charged groups.