Extended Data Fig. 8. Contact lifetime heatmaps.

Average lifetime of residue-residue contacts from 6 simulations of the ProTα-H1 dimer (a) and the dense-phase simulation (b). Numbers along the bottom and left denote the residue numbers of ProTα and H1, respectively. Orange rectangles denote the globular domain (GD) of H1 (residues 22 to 96). Frequency of contacts (i.e. the number of newly formed contacts by one ProTα per nanosecond) calculated from dimer and dense phase simulations are shown in (c), and (d), respectively. Blue and red bars at the top and on the right side of the plots denote positively and negatively charged residues of ProTα and H1, respectively. In general, the N-terminal part of ProTα makes fewer contacts than the rest of the chain both in the dimer and dense phase simulations (see also Fig 3e), and the lifetime of those contacts is on average shorter, especially in the dense-phase simulation. As is obvious from (d), contacts between oppositely charged residues are most frequent. White regions in a and c correspond to reside-residue combinations that were never formed during the simulations. White regions are particularly frequent in the GD, since it remains folded during the dimer simulations (Extended Data Fig. 7b). Some of the GD residues make relatively long-lived contacts, but those contacts are infrequent. In contrast to the dimer simulations, some residues of the GD do form contacts with ProTα residues in the dense phase simulation, since a small fraction of partially unfolded GDs are populated (Extended Data Fig. 7b), as expected from the low equilibrium stability of the GD(Martinsen et al. 2022; Borgia et al. 2018). e-h. Residue type-specific contact lifetime heatmaps. Average lifetimes of residue-residue contacts in the ProTα-H1 dimer (e) and the dense-phase simulations (f) classified by residue types. Excess population of contacts for specific residue pairs in the ProTα-H1 dimer (g) and in the dense-phase simulation (h) (see Methods for details). i. Numbers of contacts for specific residue types in ProTα (red) and H1 (blue). Residue pairs that are never observed (white squares) and extremely long-lived pairs (dark blue) in (e) correspond to residue types that are infrequent in the ProTα and H1 sequence (compare with i). In the dense phase, Arg forms contacts that are on average longer-lived than any other residue (F), in line with the phase separation-promoting role of Arg(Boeynaems et al. 2017; Qamar et al. 2018; Paloni, Bussi, and Barducci 2021; Vernon et al. 2018; Wang et al. 2018). The excess populations (see Methods) of contacts for specific residue pairs suggest that the interactions between charged residues are the most favorable interactions both in the dimer and in the dense-phase simulations. Note that the oppositely charged residues Glu (most abundant residue in ProTα) and Lys (most abundant residue in H1) form the largest number of contacts (g,h) but have lifetimes comparable to other residue pairs (e,f).