{
  "abstract": "Thermodynamically favoured molecular computing encodes algorithmic solutions into ground-state equilibrium configurations of self-assembling DNA nanostructures, circumventing the dissipation bounds of non-equilibrium kinetic proofreading. However, practical scaling on biologically derived scaffolds (such as single-stranded M13 bacterio- phage DNA) has been severely constrained by heterogeneous base compositions that create energetic traps, kinetic stalls along long carry runs, and uncharacterized steric effects. Here, we present a multi-scale high-performance computational study uniting coarse-grained 3D molecular dynamics (oxDNA2), combinatorial Monte Carlo free- energy flattener algorithms, and continuous-time Gillespie kinetic Monte Carlo (KMC) simulations. From 3D trajectories of assembled 4-position complexes, we demonstrate that adjacent bound compute domains remain separated by an average physical distance of 18.43± 5.58 nm with zero direct contact probability, establishing that proofreading proceeds exclusively through solution-phase tile displacement rather than on-scaffold branch migration. By integrating the spatial probability density of the flexible single- stranded arms (RMSF = 10.14 nm), we extract an effective local concentration of Ceff = 63.37 µM, explaining a 63-fold kinetic acceleration that powers the directional assembly ratchet. We resolve the failure of naive global sequence flattening by discovering a hierarchical design window (∆G◦ scaffold ≈ −18.5 kcal/mol), which homogenizes scaffold duplex variances (σ = 0.61 kcal/mol) while preserving a critical 12.7 kcal/mol free-energy gap for error discrimination. Finally, across full 25-bit binary addition problems, we demonstrate that a non-linear dwell annealing schedule enables robust",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemistry",
    "Indian Institute of Technology Kanpur"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 1,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Sharif Ahmad Naikoo",
      "orcid": "0000-0002-7792-9278"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/68pe10ksrqhcg.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15010917/v1",
  "fulltext_url": null,
  "id": "68pe10ksrqhcg",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010917/v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|DNA and Biological Computing"
    ]
  ],
  "openalex": "W7223275722",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15010917/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-22",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/68pe10ksrqhcg.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:26Z",
      "native_id": "10.26434/chemrxiv.15010917",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010917/v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|DNA and Biological Computing",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Microscopic Free-Energy Landscaping and Coarse-Grained 3D Dynamics of Scaffolded DNA Computers: Overcoming Kinetic Traps at Scale",
  "title_text": "Microscopic Free-Energy Landscaping and Coarse-Grained 3D Dynamics of Scaffolded DNA Computers: Overcoming Kinetic Traps at Scale",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:26Z",
  "url": "https://research.draconitic.com/paper/68pe10ksrqhcg",
  "venue": "ChemRxiv",
  "versions": []
}