(410a) Exploring the Conformations of Polyampholyte Necklaces: From Charge-in-Beads to Charge-in-Strings and Hierarchical Structures

Intrinsically disordered proteins are crucial for various biological processes and can be viewed as bio-relevant polyampholytes. However, how the sequence and solvent quality govern their conformations is not clear. Previous work [1] provided scaling predictions for single-chain conformations of charge-imbalanced Markov polyampholytes in theta solvent. It was predicted that polyampholyte necklaces with varying sequence blockiness would exhibit two distinct conformations: charge-in-beads necklaces and charge-in-strings necklaces. These two types of necklaces would result in different scaling laws for their structural properties. However, the derived scaling laws have been never tested in simulations. Furthermore, these considerations were limited to theta solvents only, while usually intrinsically disordered proteins are in good solvents or poor solvents. The present work is aimed to address these two challenges.

Using computer simulations, we confirmed the conformation of the new charge-in-string necklaces and the non-monotonic scaling behaviour of the number of beads. We carry out molecular dynamics simulations of charge-imbalanced Markov polyampholytes with different sequences and perform clustering analysis to characterize the necklace structure by counting the number of globular beads. To the best of our knowledge, the new type of charge-in-strings necklace is detected in simulations at certain charge blockiness for the first time. As the charge blockiness increases, the crossover between charge-in-beads and charge-in-strings necklaces occurs, which is accompanied by a non-monotonic change in the number of globular beads. This nontrivial non-monotonic behavior is consistent with the theoretical predictions of ref. [1].

Further, we extend our theoretical framework to arbitrary solvent quality. Under poor solvent conditions and at sufficiently high charge blockiness, a scaling region is found where a new, hierarchical type of necklace is predicted. These hierarchical necklaces contain beads of two different sizes, large almost neutral beads and small beads with excess charge. Large beads are analogous to that forming under theta solvent conditions. They are connected by strings carrying excess charge of the main necklace. In theta solvent, these strings would have conformations of extended polyelectrolytes, but under poor solvent conditions, they become necklaces themselves. Beads in these strings are analogous to the beads in the necklaces of hydrophobic polyelectrolytes. [2] Thus, these hierarchical structures with different types of beads can be viewed as small classical necklaces forming within the strings of the main necklaces, which are of the new type. We believe that our findings can be helpful for understanding the principles of controlling the conformations of IDPs and provide useful guidelines for the design of complex and tunable polyampholyte-based materials.

[1] Rumyantsev, A. M.; Johner, A.; de Pablo, J. J. Sequence blockiness controls the structure of polyampholyte necklaces. ACS Macro Letter 2021, 10, 1048−1054.

[2] Dobrynin, A. V.; Rubinstein, M.; Obukhov, S. P. Cascade of transitions of polyelectrolytes in poor solvents. Macromolecules 1996, 29, 2974−2979.