{
  "abstract": "Motivation: Accurate prediction of mutation-induced protein--protein binding free-energy changes is important for antibody affinity maturation, yet scarce labels and complex interface geometry limit generalization. Heterogeneous predictors may process three-dimensional complexes without preserving the cross-chain signals most relevant to a mutation in their final scalar output. Results: We introduce CIR-DDG, a lightweight residual adapter that combines a fixed base prediction with 22 interpretable descriptors of cross-chain distance, contact density and site--partner context. In complex-level five-fold evaluation on SKEMPI 2.0 measurements from 343 complexes, CIR-DDG improved all six tested backbones on antibody--antigen interface mutations: Spearman correlation increased by 0.0346--0.1296, while RMSE decreased by 0.0074--0.0408\\kcalmol. Cross-validated probing, equal-capacity controls and feature ablations support the complementarity of explicit geometry. On an independent SARS-CoV-2 RBD--ACE2 deep-mutational-scan benchmark of 3669 substitutions, the fold-specific adapters transferred without any retraining: the absolute interface Spearman correlation increased by 0.026--0.081 for all four evaluable backbones, showing that the learned geometric correction generalizes beyond SKEMPI thermodynamic measurements. Availability and implementation: CIR-DDG is available at https://github.com/ecnuabmlab/CIR-ddG.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": "2608.27530",
  "author_total": 9,
  "authors": [
    {
      "name": "Weilun Yu"
    },
    {
      "name": "Zhiheng Zou"
    },
    {
      "name": "Yonggui Huang"
    },
    {
      "name": "Honggang Qi"
    },
    {
      "name": "Geguang Pu"
    },
    {
      "name": "Yu Xiao"
    },
    {
      "name": "Gang Xu"
    },
    {
      "name": "Jiangtao Wang"
    },
    {
      "name": "Xi Chen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/60x86jta3h0g4.bib",
  "cited_by": 0,
  "doi": "10.48550/arxiv.2608.27530",
  "fulltext_url": null,
  "id": "60x86jta3h0g4",
  "issns": [],
  "landing_url": "https://arxiv.org/abs/2608.27530",
  "language": null,
  "licence": "LicenseRef-arXiv-nonexclusive-1.0",
  "licence_label": "arXiv licence",
  "licence_source": "article",
  "licence_url": "http://arxiv.org/licenses/nonexclusive-distrib/1.0/",
  "metadata_licence": "CC0-1.0",
  "native_subjects": [
    [
      "arxiv",
      "q-bio.QM"
    ],
    [
      "openalex",
      "1312|Protein Structure and Dynamics"
    ]
  ],
  "openalex": "W7204809562",
  "pdf_url": "https://arxiv.org/pdf/2608.27530",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-27",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/60x86jta3h0g4.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:29Z",
      "native_id": "2608.27530",
      "source": "arxiv",
      "url": "https://arxiv.org/abs/2608.27530"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "arxiv:q-bio.QM",
      "subfield": "bioinformatics"
    }
  ],
  "title": "CIR-DDG: backbone-agnostic residual correction of antibody-antigen affinity changes with explicit cross-chain geometry",
  "title_text": "CIR-DDG: backbone-agnostic residual correction of antibody-antigen affinity changes with explicit cross-chain geometry",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:29Z",
  "url": "https://research.draconitic.com/paper/60x86jta3h0g4",
  "venue": "arXiv",
  "versions": []
}