{
  "abstract": "Background/Objectives: Maresin 1 (MaR1), a pro-resolving mediator derived from docosahexaenoic acid (DHA), differs from DHA in its C7/C14 hydroxylation pattern and double-bond arrangement. We compared their recognition by peroxisome proliferator-activated receptor α (PPARα), peroxisome proliferator-activated receptor γ (PPARγ), and retinoic acid receptor-related orphan receptor α (RORα) in the context of metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: We validated Glide docking by redocking reference ligands and performed four independent 250 ns molecular dynamics simulations per complex (24 trajectories; 6.0 μs). We evaluated structural stability, replica-resolved contacts, oxygen distance profiles, and conformational sampling; relative energetic estimates were obtained using molecular mechanics/generalized Born surface area (MM-GBSA) calculations. Results: Redocking RMSDs were ≤1.5 Å, and the replicated trajectories showed no ligand dissociation. In PPARα, MaR1 showed recurrent C7-OH–Lys358 proximity and reproducible carboxylate-associated contacts with Tyr314 and Ser280. In PPARγ, the MaR1 carboxylate sampled Tyr473 in helix 12 and HIE323 with replica-dependent geometry, whereas DHA retained an Arg288-centered anchor. In RORα, MaR1 preferentially sampled an Arg370-centered arrangement, whereas DHA predominantly engaged Arg367; both ligands displayed replica-dependent alternative polar contacts. MaR1 showed more negative hydrogen-bonding, lipophilic, and van der Waals contributions and lower numerical total MM-GBSA scores than DHA across all three receptor pairs. Conclusions: MaR1 showed receptor-specific redistribution of polar contacts associated with alternative carboxylate positioning. Although the calculations do not establish binding affinity or receptor activation, these patterns, rather than a conserved direct C7-OH/C14-OH recognition motif, define testable interaction sites for matched-analog studies and functional assays.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratory of Pharmacology and Physiology, Department of Basic Biomedical Sciences, Faculty of Health Sciences, University of Talca, Talca 3460000, Chile",
    "Doctorate in Science Program, Mention in Research and Development of Bioactive Products, Institute of Chemistry of Natural Resources, University of Talca, Talca 3460000, Chile",
    "Laboratory of Molecular Physiology, Faculty of Medicine, University of Talca, Talca 3460000, Chile",
    "Doctorate in Biomedical Sciences Program, Faculty of Health Sciences, University of Talca, Talca 3460000, Chile",
    "Department of Preclinical Sciences, Faculty of Medicine, Catholic University of Maule, Talca 3460000, Chile"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Matías Quiñones San Martín",
      "orcid": "0000-0002-6320-7450"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Christian Olivera-Fuentes",
      "orcid": "0009-0001-4600-0511"
    },
    {
      "affs": [
        0
      ],
      "name": "Francisca Herrera-Vielma"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Ramón Norambuena-González",
      "orcid": "0009-0002-9065-7294"
    },
    {
      "affs": [
        4
      ],
      "name": "Eduardo Solís-Céspedes",
      "orcid": "0000-0002-7834-524X"
    },
    {
      "affs": [
        0
      ],
      "name": "Daniel R. González",
      "orcid": "0000-0002-3437-8998"
    },
    {
      "affs": [
        0
      ],
      "name": "Yunier Perera-Sardiña",
      "orcid": "0000-0001-8205-2565"
    },
    {
      "affs": [
        0
      ],
      "name": "Jessica Zúñiga-Hernández",
      "orcid": "0000-0003-2930-991X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bjkg8hnje1fr2.bib",
  "cited_by": 0,
  "doi": "10.3390/biom16111558",
  "fulltext_url": null,
  "id": "bjkg8hnje1fr2",
  "issns": [
    "2218-273X"
  ],
  "landing_url": "https://www.mdpi.com/2218-273X/16/11/1558",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Peroxisome Proliferator-Activated Receptors"
    ]
  ],
  "openalex": "W7223818977",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-26",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/bjkg8hnje1fr2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:59Z",
      "native_id": "10.3390/biom16111558",
      "source": "crossref",
      "url": "https://www.mdpi.com/2218-273X/16/11/1558"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Peroxisome Proliferator-Activated Receptors",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Receptor-Specific Molecular Recognition of Maresin 1 and Docosahexaenoic Acid by the Nuclear Receptors PPARα, PPARγ, and RORα",
  "title_text": "Receptor-Specific Molecular Recognition of Maresin 1 and Docosahexaenoic Acid by the Nuclear Receptors PPARα, PPARγ, and RORα",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:59Z",
  "url": "https://research.draconitic.com/paper/bjkg8hnje1fr2",
  "venue": "Biomolecules",
  "versions": []
}