Random polyampholytes (PAs) contain positively and negatively charged monomers that are distributed randomly along the polymer chain. The interaction between charges is assumed to be given by the Debye-Huckel potential. We show that the size of the PA is determined by an interplay between electrostatic interactions, giving rise to the polyelectrolyte (PE) effect due to net charge per monomer (σ), and an effective attractive PA interaction due to charge fluctuations, δσ. The interplay between these terms gives rise to non-monotonic dependence of the radius of gyration, Rg on the inverse Debye length, κ when PA effects are important . In the opposite limit, Rg decreases monotonically with increasing κ. Simulations of PA chains, using a charged bead-spring model, further corroborates our theoretical predictions. The simulations unambiguously show that conformational heterogeneity manifests itself among sequences that have identical PA parameters. A clear implication is that the phases of PA sequences, and by inference IDPs, cannot be determined using only the bare PA parameters (σ and δσ).The theory is used to calculate the changes in Rg on N, the number of residues for a set of Intrinsically Disordered Proteins (IDPs). For a certain class of IDPs, with N between 24 to 441, the size grows as Rg ~ N0.6, which agrees with data from Small Angle X-ray Scattering (SAXS) experiments.
Net charge per residue modulates conformational ensembles of intrinsically disordered proteins
