Role of Strong Localized vs. Weak Distributed Interactions in Disordered Protein Phase Separation Institutional Repository Document uri icon


  • AbstractInteraction strength and localization are critical parameters controlling the single-chain and condensed-state properties of intrinsically disordered proteins (IDPs). Here, we decipher these relationships using coarse-grained heteropolymers comprised of hydrophobic (H) and polar (P) monomers as model IDPs. We systematically vary the fraction of P monomersXPand employ two distinct particle-based models that include either strong localized attractions between only HH pairs (HP model) or weak distributed attractions between both HH and HP pairs (HP+ model). To compare different sequences and models, we first carefully tune the attraction strength for all sequences to match the single-chain radius of gyration. Interestingly, we find that this procedure produces similar conformational ensembles, nonbonded potential energies, and chain-level dynamics for single chains of almost all sequences in both models, with some deviations for the HP model at largeXP. However, we observe a surprisingly rich phase behavior for the sequences in both models that deviates from the expectation that similarity at the single-chain level will translate to similar phase-separation propensity. Coexistence between dilute and dense phases is only observed up to a model-dependentXPdespite the presence of favorable interchain interactions, which we quantify using the second virial coefficient. Instead, the limited number of attractive sites (H monomers) leads to the self-assembly of finite-sized clusters of different sizes depending onXP. Our findings strongly suggest that models with distributed interactions favor the formation of liquid-like condensates over a much larger range of sequence compositions compared to models with localized interactions.

altmetric score

  • 10.2

author list (cited authors)

  • Rekhi, S., Devarajan, D. S., Howard, M. P., Kim, Y. C., Nikoubashman, A., & Mittal, J.

citation count

  • 5

complete list of authors

  • Rekhi, Shiv||Devarajan, Dinesh Sundaravadivelu||Howard, Michael P||Kim, Young C||Nikoubashman, Arash||Mittal, Jeetain

Book Title

  • bioRxiv

publication date

  • January 2023