ArticleBiomacromolecules2025
Understanding Biases in Liquid-Liquid Phase Separation: Investigating Amino Acid Enrichments in Phase-Separating Proteins toward Peptide Design.
Article in Biomacromolecules, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Diverging Liquid-Liquid Phase Separation Behavior of Different Recombinant Major Ampullate Spidroins.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- From dynamic condensates to pathological assemblies: the phase behavior of tau andFrontiers in molecular neuroscience · 2026Review
- Computational investigation of the sequence context of arginine/glycine-rich motifs in the human proteome.BMC genomics · 2025Article
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Authors and funding
6 authors.
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Abstract
Liquid-liquid phase separation (LLPS) facilitates the formation of membraneless organelles, enhancing biochemical processes. The stickers-and-spacers model explains LLPS but is mainly validated in prion-like RNA-binding proteins. To broaden our understanding, we investigated peptide motifs associated with LLPS across diverse protein contexts using a computational approach on the droplet-promoting regions (DPRs) of 178 phase-separating proteins. The study identified 129 enriched peptide motifs (3-6 residues), characterized by Gly-rich sequences interspersed with aromatic, charged, and polar residues, as well as homopeptide repeats (e.g., GGDR, SRGG, QQQQ). Analysis of motif presence and frequency revealed a widespread distribution across DPRs and significant repetitive patterns. Motif trios with a higher likelihood of co-occurrence were utilized in a data-driven approach to design peptides with LLPS propensity. The designed peptides exhibited liquid-like behavior with different dynamics upon experimental validation. This work provides insights into sequence determinants of phase separation and offers the potential for designing synthetic condensates with tailored properties.
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