{
  "abstract": "We present SOP-Multi-{pi}, an enhanced version of the two-bead-per-amino-acid resolution Self-Organized Polymer (SOP) model designed to investigate the conformational dynamics of Intrinsically Disordered Proteins (IDPs) and their phase behavior in biomolecular condensates. The original SOP-IDP and SOP-Multi models work well for chains in good solvents that predominantly adopt expanded conformations. However, they fail to reproduce the single-chain properties and phase-separation behavior of IDPs such as hnRNPA1 and its variants, which have a distinct pattern of aromatic residues. We therefore reparameterized the SOP-IDP force field to explicitly capture {pi}-{pi} and cation-{pi} interactions at the coarse-grained (CG) resolution. These interactions are weak but important for biomolecular recognition and for driving and stabilizing biomolecular condensates. Dimensionless rescaling prefactors ({lambda}) were applied exclusively to the aromatic {pi}-{pi} (Phe, Tyr, Trp) and cation-{pi} (Arg/Lys with Phe, Tyr, Trp) pairs. They were optimized iteratively against experimental radii of gyration of the hnRNPA1 low-complexity domain (A1-LCD) and its 16 aromatic and charge mutants. This restored a physically meaningful Tyr > Phe interaction hierarchy, and the Pearson correlation for Rg improved from r = 0.07 (SOP-IDP) to r = 0.83 (RMSD = 0.08 nm). The same parameters, without further tuning, gave r = 0.93 for 34 additional IDPs (24-198 residues) and reproduced Flory scaling ( {nu} ~ 0.588). We back-mapped microsecond-scale CG ensembles to all-atom representations and computed SAXS and Kratky profiles for direct comparison with experiments on IDPs and on the multidomain proteins hnRNPA1, TDP-43, G3BP1, and FUS. In direct-coexistence slab simulations, the model captures the phase behavior of A1-LCD condensates and their variants, with critical temperatures that correlate strongly with experiment (r = 0.88) but are somewhat underestimated in absolute terms. The model is implemented in LAMMPS, and a detailed user manual is provided for setting up single-chain and multi-chain condensate simulations of full-length multidomain proteins.",
  "abstract_shown": true,
  "affiliations": [
    "Indian Institute of Science"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "name": "S. Prajapati"
    },
    {
      "name": "N. Mathur"
    },
    {
      "name": "D. Chakraborty"
    },
    {
      "affs": [
        0
      ],
      "name": "A. Srivastava"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/83vxwyd985n8j.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.30.755554",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.30.755554v1.full",
  "id": "83vxwyd985n8j",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.30.755554v1",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biophysics"
    ],
    [
      "openalex",
      "1312|Protein Structure and Dynamics"
    ]
  ],
  "openalex": "W7215085092",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.30.755554v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-30",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/83vxwyd985n8j.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:25:42Z",
      "native_id": "10.64898/2026.09.30.755554",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.30.755554v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biophysics",
      "subfield": "biophysics"
    }
  ],
  "title": "SOP-Multi-π: A Two-Site Coarse-Grained Model with Rescaled Aromatic Interactions to Bridge Single-Chain Ensembles and Condensate Phase Behavior of IDPs and Multidomain Proteins",
  "title_text": "SOP-Multi-π: A Two-Site Coarse-Grained Model with Rescaled Aromatic Interactions to Bridge Single-Chain Ensembles and Condensate Phase Behavior of IDPs and Multidomain Proteins",
  "type": "preprint",
  "updated_at": "2026-10-30T12:25:42Z",
  "url": "https://research.draconitic.com/paper/83vxwyd985n8j",
  "venue": "bioRxiv",
  "versions": []
}