{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T06:07:44Z","timestamp":1779084464614,"version":"3.51.4"},"reference-count":137,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioinform."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Hepatocellular carcinoma (HCC) is among the deadliest cancers, and current biomarkers offer limited diagnostic and therapeutic utility. Identifying novel druggable targets remains a critical challenge for improving HCC management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We implemented an omics-guided computational pipeline integrating single-cell RNA sequencing (scRNA-seq), differential gene expression (DGE) analysis, UMAP clustering, and protein\u2013protein interaction (PPI) network mapping to prioritize candidate genes. Structural characterization of the selected target was performed using AlphaFold-derived models followed by long-timescale molecular dynamics (MD) simulations. Virtual screening of the PeruNPDB (Peruvian Natural Products Database) was conducted using Glide docking, with further evaluation by MM-GBSA and MD-based interaction analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among prioritized genes (TMBIM4, RGS5, CEACAM7, and VCX2), the cancer\/testis antigen VCX2 emerged as a promising candidate due to its aberrant expression and potential involvement in chromosomal instability. MD refinement yielded a stable and ligand-accessible VCX2 conformation. Virtual screening identified luteolin-5-O-glucoside from\n                      <jats:italic>Equisetum arvense<\/jats:italic>\n                      as the top ligand (Glide score: \u22123.949 \u00b1 0.85 kcal\/mol; \u0394G\n                      <jats:sub>bind<\/jats:sub>\n                      : \u221235.43 \u00b1 1.12 kcal\/mol). Despite a modest docking score, consistent with the shallow and polar binding site, MM-GBSA and MD simulations supported a thermodynamically favorable and dynamically stable interaction. Key hydrogen bonds with residues Glu68, Thr63, and Ala61 were maintained within a stabilized polar groove.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings support VCX2 as a potential molecular target in HCC and highlight luteolin-5-O-glucoside as a promising lead scaffold. This study provides a hypothesis-generating framework that integrates single-cell transcriptomics with structure-based druggability analysis, offering new avenues for targeted therapeutic development in HCC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fbinf.2026.1822441","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T05:42:24Z","timestamp":1779082944000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["An integrative omics-guided druggability analysis of VCX2 in hepatocellular carcinoma using Peruvian natural products"],"prefix":"10.3389","volume":"6","author":[{"given":"Luis Daniel","family":"Goyzueta-Mamani","sequence":"first","affiliation":[{"name":"Computational Biology and Chemistry Research Group, Vicerrectorado de Investigaci\u00f3n, Universidad Cat\u00f3lica de Santa Mar\u00eda","place":["Arequipa, Peru"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruna Luz","family":"Barazorda-Ccahuana","sequence":"additional","affiliation":[{"name":"Computational Biology and Chemistry Research Group, Vicerrectorado de Investigaci\u00f3n, Universidad Cat\u00f3lica de Santa Mar\u00eda","place":["Arequipa, Peru"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mayron Antonio","family":"Candia-Puma","sequence":"additional","affiliation":[{"name":"Computational Biology and Chemistry Research Group, Vicerrectorado de Investigaci\u00f3n, Universidad Cat\u00f3lica de Santa Mar\u00eda","place":["Arequipa, Peru"]},{"name":"Facultad de Ciencias Farmac\u00e9uticas, Bioqu\u00edmicas y Biotecnol\u00f3gicas, Universidad Cat\u00f3lica de Santa Mar\u00eda","place":["Arequipa, Peru"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadia M.","family":"Hamdy","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology Department Faculty of Pharmacy, Ain Shams University","place":["Cairo, Egypt"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel Angel","family":"Ch\u00e1vez-Fumagalli","sequence":"additional","affiliation":[{"name":"Computational Biology and Chemistry Research Group, Vicerrectorado de Investigaci\u00f3n, Universidad Cat\u00f3lica de Santa Mar\u00eda","place":["Arequipa, Peru"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1388294","DOI":"10.3389\/fmolb.2024.1388294","article-title":"RNA-binding protein transcripts as potential biomarkers for detecting Primary sclerosing cholangitis and for predicting its progression to cholangiocarcinoma","volume":"11","author":"Ala","year":"2024","journal-title":"Front. 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