Cooperative nature of residue interactions in biomolecular condensates
- 1School of Physics, Zhejiang University, Hangzhou 310058, China
- 2Department of Physics, Hong Kong Baptist University, Kowloon Tong, Hong Kong 999077, China
- 3Institute for Advanced Study in Physics, Zhejiang University, Hangzhou 310058, China
Abstract
Cooperativity of residue interactions is prevalent in proteins and plays an essential role in protein folding. However, whether cooperativity exists in intrinsically disordered proteins (IDPs) and their assembled biomolecular condensates remains elusive. Here, we reveal the presence of residue interaction cooperativity in various IDP condensates using atomistic molecular dynamics simulations. In all these condensates, cooperative residue interactions manifest as packing between finite residue motifs (3 to 5 residues) with lifetimes three orders of magnitude longer than residue contacts. Notably, these higher-order interactions (HOIs) exhibit a significant nonadditive free energy, which originates from a local low-dielectric environment. The underlying sequence patterns like “Y-X-Q”, “D-X-R”, and “S-Y-X” are identified. Furthermore, HOIs dominate the cohesive energy of IDPs and condensates can be treated as HOI-crosslinked networks. This model can successfully reproduce experimental results of condensate physical properties, including saturation concentration, viscoelasticity, and interfacial tension.
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BibTeX
@article{chen2026cooperative,
title = {{Cooperative nature of residue interactions in biomolecular condensates}},
author = {Le Chen and Xiangyu Wu and Guorong Hu and Xiangze Zeng and Jingyuan Li},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2026},
month = oct,
doi = {10.1073/pnas.2618489123},
url = {https://doi.org/10.1073/pnas.2618489123},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Cooperative nature of residue interactions in biomolecular condensates
AU - Le Chen
AU - Xiangyu Wu
AU - Guorong Hu
AU - Xiangze Zeng
AU - Jingyuan Li
PY - 2026
DA - 2026/10/28
JO - Proceedings of the National Academy of Sciences of the United States of America
DO - 10.1073/pnas.2618489123
UR - https://doi.org/10.1073/pnas.2618489123
AB - Cooperativity of residue interactions is prevalent in proteins and plays an essential role in protein folding. However, whether cooperativity exists in intrinsically disordered proteins (IDPs) and their assembled biomolecular condensates remains elusive. Here, we reveal the presence of residue interaction cooperativity in various IDP condensates using atomistic molecular dynamics simulations. In all these condensates, cooperative residue interactions manifest as packing between finite residue motifs (3 to 5 residues) with lifetimes three orders of magnitude longer than residue contacts. Notably, these higher-order interactions (HOIs) exhibit a significant nonadditive free energy, which originates from a local low-dielectric environment. The underlying sequence patterns like “Y-X-Q”, “D-X-R”, and “S-Y-X” are identified. Furthermore, HOIs dominate the cohesive energy of IDPs and condensates can be treated as HOI-crosslinked networks. This model can successfully reproduce experimental results of condensate physical properties, including saturation concentration, viscoelasticity, and interfacial tension.
SN - 0027-8424
SN - 1091-6490
ER -