Conformations of Sequence-Specific Polyampholytes with Zero and Nonzero Global Charges

This work combines scaling theory and coarse-grained simulations to reveal how monomer sequences control single-chain conformational behaviors of PAs in salt-free solutions. We consider PAs with the charge statistics given by the first-order Markov process. In these PAs, charge “blockiness” is defined by the correlation λ along the chain. Markov sequences cover a wide spectrum of sequences ranging from alternating (λ = −1) to ideally random (λ = 0) to diblock PA for the charge-balanced case or (homo)polyelectrolyte for the charge-imbalanced case (λ → 1).

In the first part of the work, we consider globally neutral PAs with zero net charges. We demonstrate that any sufficiently long PAs form globules under theta solvent conditions, but the physical properties of these globules are strongly sequence-dependent. The higher the clustering of the opposite charges, i.e., the value of λ, the higher the density of the PA globule. We distinguish three different scaling regimes, which correspond to almost alternating, substantially random. and highly blocky polyampholytes. The predicted scaling laws for the dimensions of the PA globules in these regimes are confirmed coarse-grained molecular dynamics simulations.

The second part of the present work is devoted to charge-imbalanced Markov PAs. In this case, the global charge of PAs results in their pearl-necklace, tadpole-like, or fully stretched (polyelectrolyte-like) conformations. The developed scaling approach shows that the formation, structure, and dimensions of PA necklaces are controlled by the charge statistics. The sequence-dependent structure of PA necklaces is supported by coarse-grained simulations. The present work provides an insight into sequence-encoded conformations and conformational transitions in single-chain synthetic PAs and intrinsically disordered proteins (IDPs).