{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T15:10:35Z","timestamp":1779289835113,"version":"3.51.4"},"reference-count":40,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hyperoxaluria Type 1 (PH1) is a rare autosomal recessive metabolic disorder caused by mutations in the AGXT gene, leading to impaired glyoxylate metabolism and excessive oxalate accumulation, resulting in nephrolithiasis, nephrocalcinosis, and end-stage renal disease. As a rare and often neglected disease, PH1 poses a significant challenge to modern healthcare systems due to its progressive nature and limited therapeutic options. In this study, an integrated in silico approach was employed to identify pathogenic single-nucleotide polymorphisms (SNPs) and evaluate potential therapeutic candidates. Computational analyses using ConSurf, Align-GVGD, INPS-MD, CUPSAT, and iStable identified G161C and Y260C as highly deleterious variants affecting protein stability. Virtual screening, followed by ADME and toxicity assessments, identified Tauroursodeoxycholic acid (TUDCA) as a promising candidate with favorable pharmacokinetic and safety profiles. Molecular docking revealed that TUDCA exhibited higher binding affinity than the reference drug pyridoxine across native and SNP variants of AGXT proteins. Molecular dynamics simulations (300 ns) demonstrated enhanced structural stability of TUDCA-bound complexes, indicated by reduced RMSD and RMSF, improved compactness, and sustained hydrogen bonding. Furthermore, free energy landscape (FEL) and dynamic cross-correlation matrix (DCCM) analyses confirmed improved conformational stability and coordinated residue motions in SNP variant structures. Overall, these findings suggest that TUDCA may effectively stabilize structural alterations induced by pathogenic AGXT variants, highlighting its potential as a precision medicine-based therapeutic strategy for PH1.<\/jats:p>","DOI":"10.3390\/ijms27104590","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T14:12:54Z","timestamp":1779286374000},"page":"4590","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting the Highly Deleterious G161C and Y260C SNP Variants of the AGXT Protein Involved in Glyoxylate Metabolism Using Tauroursodeoxycholic Acid: A Computational Study"],"prefix":"10.3390","volume":"27","author":[{"given":"Shruthika","family":"Giridharan","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Faculty of Biomedical Sciences & Technology, Sri Ramachandra Institute of Higher Education and Research (DU), Chennai 600116, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasundra","family":"Vasudevan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Faculty of Biomedical Sciences & Technology, Sri Ramachandra Institute of Higher Education and Research (DU), Chennai 600116, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9202-2201","authenticated-orcid":false,"given":"Sidharth Kumar","family":"Nanda Kumar","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Faculty of Biomedical Sciences & Technology, Sri Ramachandra Institute of Higher Education and Research (DU), Chennai 600116, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madhana Priya Nanda","family":"Kumar","sequence":"additional","affiliation":[{"name":"Center for Transdisciplinary Research, Department of Pharmacology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Chennai 600077, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9508-8097","authenticated-orcid":false,"given":"Magesh","family":"Ramasamy","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Faculty of Biomedical Sciences & Technology, Sri Ramachandra Institute of Higher Education and Research (DU), Chennai 600116, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1056\/NEJMra1301564","article-title":"Primary hyperoxaluria","volume":"369","author":"Cochat","year":"2013","journal-title":"N. 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