{
  "abstract": "Background\n\nThe widespread use of Bacillus thuringiensis (Bt) Cry toxins has led to the evolution of resistance in target insect pests, posing a significant threat to sustainable agriculture. Manduca sexta, a major pest of Solanaceae crops, is developing resistance to conventional Cry1Ac toxins, necessitating the development of novel, high-efficacy molecular alternatives.Objectives\n\nThis study aimed to design and computationally evaluate a novel hybrid toxin, RCGX1, by fusing functional domains of Cry1Ac and XptC proteins. The novelty of this approach lies in the rational fusion of domains from distinct bacterial toxin classes (Bacillus and Xenorhabdus) to create an emergent, neo-binding site, a strategy that moves beyond conventional single-toxin modifications.Materials and methods\n\nFunctional domains were identified using InterPro: the galactose-binding domain of Cry1Ac (residues 462-609) and the SpvB toxin domain of XptC (residues 32-278). These domains were fused via a flexible (SSGG)4 linker to create the hybrid protein RCGX1. The 3D structure was predicted using I-TASSER and refined through energy minimization(converging in 730 steps). The quality of the model was validated using VERIFY3D, PROCHECK, and ERRAT. Molecular dynamics (MD) simulations (200 ns) were performed using GROMACS (CHARRM 27 force field) to assess structural stability. with analyses of Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), Radius of Gyration (Rg), and hydrogen bond formation. Molecular docking by APN receptor was done using ClusPro to evaluate binding affinity and interaction sites.Results\n\nMD simulations demonstrated robust structural stability, with RMSD stabilizing at ~0.65 nm and Rg averaging 2.4 nm, indicating a compact and stable conformation. Docking revealed a high-affinity interaction (-1437.0 kcal.mol-1) unexpectedly mediated by the XptC moiety. The interface is anchored by a multivalent Arg36-Glu195 salt bridge, which is structurally reinforced by a local hydrophobic cage (Trp31/Phe34) and a specific hydrogen-bond network orchestrated by Gln125 and Gly284, creating a robust, engineered epitope distinct from canonical Cry toxins.Conclusion\n\nThe designed hybrid protein RCGX1 exhibits exceptional structural stability and a potent, specific binding affinity in silico. These results strongly suggest that RCGX1 is a compelling candidate for a new class of dual-function toxins. RCGX1 is thus positioned as a powerful lead candidate for experimental validation, offering a promising strategy capable of countering established Bt resistance pathways and paving the way for the development of next-generation biopesticides.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Plant Breeding and Biotechnology, University of Zabol, Zabol, Iran.",
    "Industrial Biotechnology Group, Biotechnology Research Center, Ferdowsi University of Mashhad, Mashhad, Iran.",
    "Laboratory of Computational Biotechnology and Bioinformatics (CBB), Department of Bioinformatics, Faculty of Basic Sciences, University of Zabol, Zabol, Iran.",
    "Department of Biology, Ferdowsi University of Mashhad, Mashhad, Iran."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Mohammad Javad Rashidabadi"
    },
    {
      "affs": [
        0
      ],
      "name": "Mahmood Solouki"
    },
    {
      "affs": [
        1
      ],
      "name": "Aliakbar Haddad-Mashadrizeh"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Abbasali Emamjomeh"
    },
    {
      "affs": [
        3
      ],
      "name": "Ali Makhdoumi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ahw4ac5f4gxrp.bib",
  "cited_by": 0,
  "doi": "10.30498/ijb.2026.554854.4284",
  "fulltext_url": "https://europepmc.org/articles/PMC13695773",
  "id": "ahw4ac5f4gxrp",
  "issns": [
    "1728-3043",
    "2322-2921"
  ],
  "landing_url": "https://europepmc.org/article/MED/42928841",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [],
  "openalex": null,
  "pdf_url": "https://europepmc.org/articles/PMC13695773?pdf=render",
  "pmcid": "PMC13695773",
  "pmid": "42928841",
  "published": "2026-10-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ahw4ac5f4gxrp.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:18Z",
      "native_id": "MED:42928841",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42928841"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "journal-openalex:F13",
      "subfield": "general"
    }
  ],
  "title": "Design and In Silico Evaluation of a Cry1Ac/XptC Hybrid Protein Targeting the APN Receptor in Manduca sexta.",
  "title_text": "Design and In Silico Evaluation of a Cry1Ac/XptC Hybrid Protein Targeting the APN Receptor in Manduca sexta.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:18Z",
  "url": "https://research.draconitic.com/paper/ahw4ac5f4gxrp",
  "venue": "Iranian journal of biotechnology",
  "versions": []
}