A Roadmap for Polyampholyte Necklaces: Effects of Charge Blockiness and Solvent Quality

Conformations of charge-imbalanced polyampholytes are governed by an interplay of non-electrostatic interactions among all the monomers and Coulomb interactions between the charged units. Non-electrostatic interactions are defined by the solvent quality, while Coulomb interactions are sensitive to their primary charge sequence. As a result, polyampholytes adopt globular or stretched or intermediate necklace conformations. To fully describe their conformational behavior, we consider chains with Markov charge statistics and construct a scaling diagram of states in coordinates of charge blockiness and solvent quality. Numerous scaling regimes of different necklaces are distinguished, classified into three types: (i) "Charge-in-beads" necklaces mostly form at moderate charge blockiness, with the bead size governed by its Rayleigh instability; (ii) "Charge-in-strings" necklaces are stable at a higher blockiness when the charge imbalance migrates from the beads to the strings; (iii) "Hierarchical" necklaces are novel necklace-in-necklace conformations comprising beads of two different sizes, which coexist at high charge blockiness and in poor solvent only. Molecular dynamics simulations are performed to support key scaling predictions. This study provides a comprehensive conformational map, enabling systematically prediction and classification the structure of intrinsically disordered proteins/regions (IDPs/IDRs).