{
  "id": 5708428,
  "title": "Hydrophobic Patch Spacing Produces Nonmonotonic Compaction in Intrinsically Disordered Proteins",
  "url": "https://urgent.news/2026/09/04/hydrophobic-patch-spacing-produces-nonmonotonic-compaction-in",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-04T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.02.748969v1?rss=1"
  },
  "original_language": "en",
  "account": "Intrinsically disordered proteins (IDPs) have conformational ensembles that depend on the distribution of physicochemical interactions along their sequences. Hydropathy-based descriptors describe average chain dimensions for diverse IDPs, but the impact of spacing localized hydrophobic patches is not well understood. By simulating fixed-composition FUS-derived sequence variants using coarse-grained models, researchers found that maximal compaction occurs at an intermediate spacing between the localized hydrophobic patches.\n\nAnalysis of simplified model peptides showed that this nonmonotonic compaction behavior falls into one of three spacing responses: monotonic expansion, nonmonotonic compaction, and monotonic compaction. The occurrence of these responses depends on interaction strength, effective interaction length scale, and patch architecture. However, nonmonotonic compaction only happens when hydrophobic attractions are strong enough.\n\nA conformational-class decomposition was used to unravel these responses into weighted contributions from patch-contact and patch-noncontact regions in the ensemble-averaged chain dimensions. In regimes where interactions are attractive, the contact contribution decreases with spacing, while the noncontact contribution increases. The changing balance between these opposing effects leads to maximal compaction at an intermediate spacing.\n\nIn contrast, steric-dominated regimes show that separating the patches actually compacts the dominant noncontact conformations by relieving steric frustration. These findings reveal that similar spacing responses can emerge from distinct microscopic mechanisms. The unified framework established by these results helps explain how interaction regime and hydrophobic patch spacing jointly shape IDP conformational ensembles.",
  "summary": "The conformational ensembles of intrinsically disordered proteins (IDPs) are encoded by the distribution of physicochemical interactions along their sequences. Although hydropathy-based descriptors capture average chain dimensions across diverse IDPs, the consequences of spacing localized hydrophobic patches remain poorly understood. Coarse-grained simulations of fixed-composition FUS-derived…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}