Skip to content
DraconiticResearch
Search Sources API
190,860 studies31 sourcesUpdated 16 min ago
Peer-reviewedCC BY-NC-NDCommunications Chemistry

Molecular determinants of arginine versus lysine cation–π interactions in biomolecular condensates

  • Lydia Armentia1
  • Xabier López2
  • David De Sancho3
  1. 1Polimero eta Material Aurreratuak: Fisika, Kimika eta Teknologia, Kimika Fakultatea, UPV/EHU & Donostia International Physics Center (DIPC), Euskadi, Spain
  2. 2Polimero eta Material Aurreratuak: Fisika, Kimika eta Teknologia, Kimika Fakultatea, UPV/EHU & Donostia International Physics Center (DIPC), Euskadi, Spain. [email protected]
  3. 3Polimero eta Material Aurreratuak: Fisika, Kimika eta Teknologia, Kimika Fakultatea, UPV/EHU & Donostia International Physics Center (DIPC), Euskadi, Spain. [email protected]
Open at sourceDOICite

Abstract

Biomolecular condensates formed by intrinsically disordered regions of proteins are primarily stabilised by specific types of amino acids, usually labelled “stickers” for their ability to crosslink distinct polypeptide chains into droplet-spanning networks. Both aromatic and positively charged residues can play this role, but they differ in their interaction types and relative strengths. An outstanding problem is the quantification of these differences, since they determine the fate of multicomponent mixtures. Here we focus on the interactions formed by aromatic residues with the two main positively charged stickers, Arg and Lys, whose experimental behaviour in condensates shows a clear hierarchy: Arg is consistently observed to promote phase separation more effectively than Lys. We use molecular dynamics simulations and alchemical transformations together with quantum chemical calculations to resolve the differences in their cation– π interaction strengths in different media. We find that, unlike the aromatic residues Phe and Tyr, Arg and Lys consistently maintain a hierarchy of interaction strengths across molecular environments, with Arg being favoured over Lys. While cation- π interactions are important, the primary factor underlying this difference is the higher dehydration penalty of Lys. By contrast, the identity of the aromatic partner that forms the strongest interaction with a cation depends on the dielectric environment. These results provide a clear molecular-level explanation for the distinct contributions of interactions between cationic and aromatic residues to condensate stability.

Related

  1. Mesoscale Heterogeneity Shapes Molecular Selectivity and Transport in Biomolecular Condensates
    V. Grigorev, Y. Zhang
    bioRxivPreprintCC BY-NC-NDFull textBiophysicsbioRxiv
  2. Molecular Flexibility and Electrostatic Interactions Drive the Nanoscale Structure of Coiled-Coil GM130 Protein Condensates
    Pablo Mateos-Gil, Alejandro Feito, Daniel González Cava +10
    PRX LifePeer-reviewedCC BY 4.0Full textMolecular biology & gene regulationHAL
  3. Long-range transport of biomolecular condensates by Marangoni effect
    Q. Guan, X. Ma, X. Guan +3
    bioRxivPreprintAll rights reservedFull textBiophysicsbioRxiv
  4. Disulfide Crosslink Density is a Key Determinant in the Formation, Dynamics, and Maturation of Cysteine-rich Designer Biomolecular Condensates.
    M. Mondal, W. S. Swetman, C. T. Allen +3
    bioRxivPreprintAll rights reservedFull textBiophysicsbioRxiv
  5. e^-2 Threshold for Bistability in Non-equilibrium Sorting of Biomolecular Condensates
    W. Chen, S. Pei, G. Yu
    bioRxivPreprintCC BY-NCFull textBiophysicsbioRxiv

Cite

BibTeXRIS
BibTeX
@article{armentia2026molecular,
  title = {{Molecular determinants of arginine versus lysine cation–π interactions in biomolecular condensates}},
  author = {Lydia Armentia and Xabier López and David De Sancho},
  journal = {Communications Chemistry},
  year = {2026},
  month = may,
  doi = {10.1038/s42004-026-02075-7},
  url = {https://doi.org/10.1038/s42004-026-02075-7},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Molecular determinants of arginine versus lysine cation–π interactions in biomolecular condensates
AU  - Lydia Armentia
AU  - Xabier López
AU  - David De Sancho
PY  - 2026
DA  - 2026/05/26
JO  - Communications Chemistry
DO  - 10.1038/s42004-026-02075-7
UR  - https://doi.org/10.1038/s42004-026-02075-7
AB  - Biomolecular condensates formed by intrinsically disordered regions of proteins are primarily stabilised by specific types of amino acids, usually labelled “stickers” for their ability to crosslink distinct polypeptide chains into droplet-spanning networks. Both aromatic and positively charged residues can play this role, but they differ in their interaction types and relative strengths. An outstanding problem is the quantification of these differences, since they determine the fate of multicomponent mixtures. Here we focus on the interactions formed by aromatic residues with the two main positively charged stickers, Arg and Lys, whose experimental behaviour in condensates shows a clear hierarchy: Arg is consistently observed to promote phase separation more effectively than Lys. We use molecular dynamics simulations and alchemical transformations together with quantum chemical calculations to resolve the differences in their cation– π interaction strengths in different media. We find that, unlike the aromatic residues Phe and Tyr, Arg and Lys consistently maintain a hierarchy of interaction strengths across molecular environments, with Arg being favoured over Lys. While cation- π interactions are important, the primary factor underlying this difference is the higher dehydration penalty of Lys. By contrast, the identity of the aromatic partner that forms the strongest interaction with a cation depends on the dielectric environment. These results provide a clear molecular-level explanation for the distinct contributions of interactions between cationic and aromatic residues to condensate stability.
SN  - 2399-3669
ER  -