{
  "abstract": "Protein-conditioned 3D molecule generation is a central challenge in structure-based drug design, requiring a balance between pocket compatibility, molecular properties, and physical geometry. We propose \\textbf{PocketVE}, a protein-pocket-conditioned variance-exploding (VE) diffusion framework that couples stable coordinate denoising with inference-time property guidance. Specifically, PocketVE combines an EDM-style training and sampling setup for 3D denoising, classifier-free guidance for multi-property steering, and adaptive protein perturbation as a training-time pocket regularizer.On the CrossDocked2020 benchmark under GenBench3D, PocketVE improves Valid$_{3\\text{D}}$ from 58.6 to 80.6 and reduces strain energy from 457.4 to 127.9 relative to its guided TAGMol architectural parent; relative to TargetDiff, it attains comparable Valid$_{3\\text{D}}$ with lower strain energy (127.9 vs.\\ 306.0), while retaining competitive docking and molecular-property scores under moderate guidance. A guidance-scale study shows that moderate guidance gives a favorable balance between target-related objectives and geometric quality, whereas stronger guidance can degrade geometry and distributional fidelity. Pocket-permutation and PoseCheck diagnostics further support pocket-specific spatial compatibility with reduced steric conflicts. Overall, the results suggest that geometric stability and inference-time property guidance should be considered as coupled design objectives.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": "2609.08101",
  "author_total": 2,
  "authors": [
    {
      "name": "Peining Zhang"
    },
    {
      "name": "Jinbo Bi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/11t4t32j73xb1.bib",
  "cited_by": 0,
  "doi": "10.48550/arxiv.2609.08101",
  "fulltext_url": null,
  "id": "11t4t32j73xb1",
  "issns": [],
  "landing_url": "https://arxiv.org/abs/2609.08101",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "http://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": "CC0-1.0",
  "native_subjects": [
    [
      "arxiv",
      "cs.LG"
    ],
    [
      "arxiv",
      "q-bio.BM"
    ],
    [
      "openalex",
      "1703|Computational Drug Discovery Methods"
    ]
  ],
  "openalex": "W7212073208",
  "pdf_url": "https://arxiv.org/pdf/2609.08101",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-27",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/11t4t32j73xb1.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:25:21Z",
      "native_id": "2609.08101",
      "source": "arxiv",
      "url": "https://arxiv.org/abs/2609.08101"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "arxiv:q-bio.BM",
      "subfield": "biophysics"
    }
  ],
  "title": "PocketVE: Stable and Property-Guided Structure-Based Drug Design with Variance-Exploding Diffusion",
  "title_text": "PocketVE: Stable and Property-Guided Structure-Based Drug Design with Variance-Exploding Diffusion",
  "type": "preprint",
  "updated_at": "2026-10-30T12:25:21Z",
  "url": "https://research.draconitic.com/paper/11t4t32j73xb1",
  "venue": "arXiv",
  "versions": []
}