Role of Strong Localized vs Weak Distributed Interactions in Disordered Protein Phase Separation. Academic Article uri icon


  • Interaction 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 monomers XP and employ two distinct particle-based models that include either strong localized attractions between only H-H pairs (HP model) or weak distributed attractions between both H-H and H-P 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 large XP. 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 a similar phase-separation propensity. Coexistence between dilute and dense phases is only observed up to a model-dependent XP, despite 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 on XP. 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.

published proceedings

  • J Phys Chem B

altmetric score

  • 2.95

author list (cited authors)

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

citation count

  • 4

complete list of authors

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

publication date

  • May 2023