{
  "abstract": "Accurate detection of leptospirosis requires high-affinity recognition of the conserved LipL32 biomarker. Although LipL32-targeting DNA aptamers have been identified through systematic evolution of ligands by exponential enrichment (SELEX), the molecular basis of their target recognition remains unclear, limiting rational post-SELEX optimization. Here, we investigated the molecular recognition mechanism of the LepDapt-5 aptamer family using molecular dynamics (MD) simulations and binding free-energy analysis. We generated three-dimensional aptamer models using AlphaFold 3 (AF3) and constructed protein–aptamer docking complexes with HADDOCK, showing a stable G-quadruplex (GQ) motif within the aptamer core. Structural and energetic analyses identified key domains contributing to LipL32 binding, while per-residue energy decomposition highlighted nucleotides suitable for rational sequence refinement. Guided by these insights, we introduced targeted single-point mutations, evaluated their effects computationally, and validated their performance experimentally using enzyme-linked aptamer sorbent assays (ELASA). Relative binding free energies (ΔΔGbind) calculated using nonequilibrium alchemical MD showed strong agreement with ELASA measurements: T19A reduced binding affinity, G7C produced minimal change, and G24C significantly enhanced affinity. Experimental equilibrium dissociation constants (KD) further supported these predictions, identifying G24C as the highest-affinity variant. Additionally, the G24C mutant retained strong binding to LipL32 while exhibiting no detectable binding to the NS1 protein of dengue virus 2 and the E2 protein of Chikungunya virus.",
  "abstract_shown": true,
  "affiliations": [
    "Thammasat University , , , ,",
    "Kanazawa University , , ,",
    "Universiti Sains Malaysia , , Bertam , , ,",
    "MILA University , , No 1, MIU Boulevard, Putra Nilai , , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Tri Cao Vu",
      "orcid": "0009-0003-9968-3859"
    },
    {
      "affs": [
        0
      ],
      "name": "Boonchoy Soontornworajit",
      "orcid": "0000-0002-2680-3456"
    },
    {
      "affs": [
        0
      ],
      "name": "Pichayanoot Rotkrua",
      "orcid": "0000-0003-2672-5782"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiraporn Arunpanichlert"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Cong Quang Vu",
      "orcid": "0000-0001-7444-9060"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Marimuthu Citartan"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuthana Tantirungrotechai",
      "orcid": "0000-0002-7162-3374"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2fe121ywzdzze.bib",
  "cited_by": 0,
  "doi": "10.1021/acsomega.6c03816",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13717746/?tool=EBI",
  "id": "2fe121ywzdzze",
  "issns": [
    "2470-1343"
  ],
  "landing_url": "https://pubs.acs.org/acsodf/article/11/42/64524/5452283/Structure-Guided-Optimization-of-a-LipL32",
  "language": "eng",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1312|Advanced biosensing and bioanalysis techniques"
    ]
  ],
  "openalex": "W7222149816",
  "pdf_url": "https://pubs.acs.org/doi/pdf/10.1021/acsomega.6c03816",
  "pmcid": "PMC13717746",
  "pmid": "42959898",
  "published": "2026-10-15",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/2fe121ywzdzze.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:39Z",
      "native_id": "10.1021/acsomega.6c03816",
      "source": "crossref",
      "url": "https://pubs.acs.org/acsodf/article/11/42/64524/5452283/Structure-Guided-Optimization-of-a-LipL32"
    },
    {
      "first_seen": "2026-10-31T00:20:37Z",
      "native_id": "PMC:PMC13717746",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13717746"
    },
    {
      "first_seen": "2026-10-31T12:21:46Z",
      "native_id": "MED:42959898",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42959898"
    },
    {
      "first_seen": "2026-11-02T12:22:00Z",
      "native_id": "PMC13717746",
      "source": "pmc",
      "url": "https://doi.org/10.1021/acsomega.6c03816"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Advanced biosensing and bioanalysis techniques",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Structure-Guided Optimization of a LipL32-Targeting DNA Aptamer through Molecular Dynamics and Free-Energy Analysis",
  "title_text": "Structure-Guided Optimization of a LipL32-Targeting DNA Aptamer through Molecular Dynamics and Free-Energy Analysis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:22:00Z",
  "url": "https://research.draconitic.com/paper/2fe121ywzdzze",
  "venue": "ACS Omega",
  "versions": []
}