{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T13:27:57Z","timestamp":1789133277530,"version":"build-2803163510"},"reference-count":70,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"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. Endocrinol."],"abstract":"<jats:p>\n                    Hypothyroidism is a condition marked by inadequate thyroid hormone production. It is typically treated with Levothyroxine, which, despite its effectiveness, can cause adverse effects on metabolism and the cardiovascular system. In this study, an in silico approach was used to screen phytochemicals from\n                    <jats:italic>Curcuma longa<\/jats:italic>\n                    ,\n                    <jats:italic>Moringa oleifera<\/jats:italic>\n                    , and\n                    <jats:italic>Nigella sativa<\/jats:italic>\n                    for their potential to activate the thyroid receptor. A total of 439 compounds were docked against Thyroid Receptor Beta 1 (TR\u03b21) and Thyrotropin-Releasing Hormone Receptor (TRHR) using AutoDock Vina. Among them, valoneic acid dilactone, curcumin III, taxifolin, luteolin, lophenol, and stigmastanol were identified from the three plants as performing better than others. These compounds were further evaluated with ADMET predictions and molecular dynamics simulations to assess their drug-like properties and stability. Lophenol from\n                    <jats:italic>Nigella sativa<\/jats:italic>\n                    showed the highest binding affinity to TR\u03b21 (-13.62 kcal\/mol) with an inhibition constant of 0.1037 nM, surpassing levothyroxine (-11.60 kcal\/mol and 6.63 nM). Also, stigmastanol from\n                    <jats:italic>Nigella sativa<\/jats:italic>\n                    showed the highest binding affinity to TRHR (-8.71 kcal\/mol) with an inhibition constant of 415 nM, surpassing levothyroxine (-7.64 kcal\/mol and 2530 nM). However, the two compounds exhibited some unfavourable ADMET properties that could be improved through formulation science. Curcumin III and taxifolin demonstrated favourable ADMET properties, including optimal solubility, lipophilicity, and polar surface area, suggesting good oral bioavailability. Molecular dynamics simulations were carried out using Desmond. The results revealed that curcumin III, lophenol, and taxifolin maintained strong stability, with RMSD values of 1.70 \u00b1 0.005 \u00c5, 2.17 \u00b1 0.012 \u00c5, and 2.50 \u00b1 0.014 \u00c5, respectively, for TR\u03b21, and RMSD values of 3.82 \u00b1 0.014 \u00c5, 4.29 \u00b1 0.019 \u00c5, and 3.31 \u00b1 0.017 \u00c5, respectively, for TRHR. This study identified Curcumin III from\n                    <jats:italic>Curcuma longa<\/jats:italic>\n                    and taxifolin from\n                    <jats:italic>Moringa oleifera<\/jats:italic>\n                    as promising natural compounds for the treatment of hypothyroidism. Further validation through\n                    <jats:italic>in vitro<\/jats:italic>\n                    ,\n                    <jats:italic>in vivo<\/jats:italic>\n                    ,\n                    <jats:italic>and ex vivo<\/jats:italic>\n                    studies is recommended.\n                  <\/jats:p>","DOI":"10.3389\/fendo.2026.1727415","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T05:19:17Z","timestamp":1771219157000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Computational screening and molecular dynamics reveal curcumin III and taxifolin as potential thyroid receptor modulators for hypothyroidism therapy"],"prefix":"10.3389","volume":"17","author":[{"given":"Babatunji Emmanuel","family":"Oyinloye","sequence":"first","affiliation":[{"name":"Institute for Drug Research and Development, S.E. Bogoro Center, Afe Babalola University","place":["Ado-Ekiti, Nigeria"]},{"name":"Phytomedicine, Biochemical Toxicology and Biotechnology Research Laboratories, Department of Biochemistry, College of Sciences, Afe Babalola University","place":["Ado-Ekiti, Nigeria"]},{"name":"Biotechnology and Structural Biology (BSB) Group, Department of Biochemistry and Microbiology, University of Zululand","place":["KwaDlangezwa, South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adetola Ibukunoluwa","family":"Adewale","sequence":"additional","affiliation":[{"name":"Institute for Drug Research and Development, S.E. Bogoro Center, Afe Babalola University","place":["Ado-Ekiti, Nigeria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalom Oluwafunke","family":"Adeyemi","sequence":"additional","affiliation":[{"name":"Institute for Drug Research and Development, S.E. Bogoro Center, Afe Babalola University","place":["Ado-Ekiti, Nigeria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omotola Martha","family":"Fajana","sequence":"additional","affiliation":[{"name":"Institute for Drug Research and Development, S.E. Bogoro Center, Afe Babalola University","place":["Ado-Ekiti, Nigeria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olutosin Samuel","family":"Olusola","sequence":"additional","affiliation":[{"name":"Institute for Drug Research and Development, S.E. Bogoro Center, Afe Babalola University","place":["Ado-Ekiti, Nigeria"]},{"name":"Department of Biology, Wake Forest University","place":["Winston Salem, NC, Nigeria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oluwatoyin Mary","family":"Oyinloye","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Sciences, Afe Babalola University","place":["Ado-Ekiti, Nigeria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aderonke Moyosola","family":"Ayeni","sequence":"additional","affiliation":[{"name":"Phytomedicine, Biochemical Toxicology and Biotechnology Research Laboratories, Department of Biochemistry, College of Sciences, Afe Babalola University","place":["Ado-Ekiti, Nigeria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayodeji Benjamin","family":"Akawa","sequence":"additional","affiliation":[{"name":"Phytomedicine, Biochemical Toxicology and Biotechnology Research Laboratories, Department of Biochemistry, College of Sciences, Afe Babalola University","place":["Ado-Ekiti, Nigeria"]},{"name":"Medical Biochemistry Unit, College of Medicine and Health Sciences, Afe Babalola University","place":["Ado-Ekiti, Nigeria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olajumoke Tolulope","family":"Idowu","sequence":"additional","affiliation":[{"name":"Industrial Chemistry Unit, Department of Chemical Sciences, College of Sciences, Afe Babalola University","place":["Ado-Ekiti, Nigeria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Austine Idowu","family":"Ibikunle","sequence":"additional","affiliation":[{"name":"Department of Community Medicine, Federal Teaching Hospital (FETHI)","place":["Ido-Ekiti, Nigeria"]},{"name":"Department of Community Medicine, College of Medicine and Health Sciences, Afe Babalola University","place":["Ado-Ekiti, Nigeria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Folake Olayinka","family":"Olojo","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, Dominion University","place":["Ibadan, Nigeria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basiru Olaitan","family":"Ajiboye","sequence":"additional","affiliation":[{"name":"Phytomedicine and Molecular Toxicology Research Laboratory, Department of Biochemistry, Federal University Oye-Ekiti","place":["Oye-Ekiti, Nigeria"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,16]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-031-74085-5_12","article-title":"Endocrine system","volume-title":"Fundamentals of medicine for biomedical engineering","author":"Hosseinzadeh","year":"2025"},{"key":"B2","doi-asserted-by":"crossref","DOI":"10.1016\/B978-0-12-801238-3.96022-7","article-title":"Thyroid gland: anatomy and physiology","volume-title":"Encyclopedia of endocrine diseases","author":"Benvenga","year":"2018"},{"key":"B3","article-title":"Embryology, Thyroid","volume-title":"StatPearls","author":"Rosen","year":"2023"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.18311\/jeoh\/2024\/36335","article-title":"Awareness of role of physiotherapy in women with hypothyroidism","volume":"24","author":"Bhalerao","year":"2024","journal-title":"J Ecophysiology Occup Health"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.46241","article-title":"Epidemiology, types, causes, clinical presentation, diagnosis, and treatment of hypothyroidism","volume":"15","author":"Zamwar","year":"2023","journal-title":"Cureus"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1080\/20786204.2012.10874256","article-title":"Hypothyroidism: an update","volume":"86","author":"Gaitonde","year":"2012","journal-title":"Am Fam Physician"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.7759\/cureus.51574","article-title":"Thyroid and its ripple effect: impact on cardiac structure, function, and outcomes","volume":"16","author":"Olanrewaju","year":"2024","journal-title":"Cureus"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2012.01.005","article-title":"Hypothyroidism: etiology, diagnosis, and management","volume":"96","author":"Almandoz","year":"2012","journal-title":"Med Clinics North America"},{"key":"B9","volume-title":"Hypothyroidea","author":"Wilson","year":"2011"},{"key":"B10","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1038\/s41572-022-00357-7","article-title":"Hypothyroidism","volume":"8","author":"Chaker","year":"2022","journal-title":"Nat Rev Dis Primers"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-012-9703-2","article-title":"The incidence and prevalence of thyroid autoimmunity","volume":"42","author":"McLeod","year":"2012","journal-title":"Endocrine"},{"key":"B12","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1007\/s12325-019-01080-8","article-title":"Hypothyroidism in context: where we\u2019ve been and where we\u2019re going","volume":"36","author":"Chiovato","year":"2019","journal-title":"Adv Ther"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(14)70225-6","article-title":"Iodine deficiency and thyroid disorders","volume":"3","author":"Zimmermann","year":"2015","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B14","doi-asserted-by":"crossref","DOI":"10.5772\/intechopen.1005431","article-title":"Hashimoto\u2019s thyroiditis","volume-title":"Hypothyroidism - causes, screening and therapeutic approaches","author":"Carkit","year":"2024"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.26479\/2018.0402.18","article-title":"Hormone imbalance\u2014A cause for concern in women","volume":"4","author":"Roop","year":"2018","journal-title":"Res J Life Sci Bioinform Pharm Chem Sci"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-023-03460-1","article-title":"Consequences of undertreatment of hypothyroidism","volume":"84","author":"Feldt-Rasmussen","year":"2024","journal-title":". Endocrine"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/J.SAJB.2019.03.021","article-title":"The miracle mix of Moringa: Status of Moringa research and development in Malawi","volume":"129","author":"Sagona","year":"2020","journal-title":"South Afr J Bot"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3390\/IJMS24032098","article-title":"Moringa oleifera: an updated comprehensive review of its pharmacological activities, ethnomedicinal, phytopharmaceutical formulation, clinical, phytochemical, and toxicological aspects","volume":"24","author":"Pareek","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B19","article-title":"Hypothyroidism: management based on ayurvedic and modern therapeutic perspective","volume":"4","author":"Kaur","year":"2016","journal-title":"Int J Pharmaceutics Drug Anal"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1515\/DMPT-2021-0136","article-title":"Efficacy and safety of Barg-e-Sahajna (Moringa oleifera Lam.) in primary hypothyroidism","volume":"37","author":"Alam","year":"2022","journal-title":"Drug Metab Pers Ther"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1155\/2024\/1270903","article-title":"Moringa oleifera: recent insights for its biochemical and medicinal applications","volume":"2024","author":"Abdelazim","year":"2024","journal-title":"J Food Biochem"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e27807","article-title":"A comprehensive review of the phytochemicals, health benefits, pharmacological safety and medicinal prospects of Moringa oleifera","volume":"10","author":"Camilleri","year":"2024","journal-title":"Heliyon"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1006\/PHRS.1999.0587","article-title":"Role of moringa oleifera leaf extract in the regulation of thyroid hormone status in adult male and female rats","volume":"41","author":"Tahiliani","year":"2000","journal-title":". Pharmacol Res"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.37506\/IJFMT.V15I3.15454","article-title":"The effect of moringa oleifera leaves powder on some hormones to prevent the development of experimental hypothyroidism in rabbits","volume":"15","author":"Hadidy","year":"2021","journal-title":"Indian J Forensic Med Toxicol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/J.PRMCM.2023.100222","article-title":"Curcuma longa (Turmeric): Ethnomedicinal uses, phytochemistry, pharmacological activities and toxicity profiles\u2014A review","volume":"6","author":"Iweala","year":"2023","journal-title":"Pharmacol Res - Modern Chin Med"},{"key":"B26","first-page":"820806","article-title":"A comprehensive review on the therapeutic potential of curcuma longa linn","volume-title":"Relation to its major active constituent curcumin. Front Pharmacol.","author":"Fuloria","year":"2022"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/J.CHNAES.2020.02.001","article-title":"Nigella sativa L.: Uses in traditional and contemporary medicines \u2013 An overview","volume":"41","author":"Majeed","year":"2021","journal-title":"Acta Ecologica Sin"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/S1875-5364(16)30088-7","article-title":"Phytochemistry, pharmacology, and therapeutic uses of black seed (Nigella sativa)","volume":"14","author":"Kooti","year":"2016","journal-title":"Chin J Nat Med"},{"key":"B29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-12-824462-3.00016-0","article-title":"History and traditional uses of black seeds (Nigella sativa)","volume-title":"Black seeds (Nigella sativa): pharmacological and therapeutic applications","author":"Dabeer","year":"2022"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/J.EUJIM.2016.03.003","article-title":"Nigella Sativa treatment and serum concentrations of thyroid hormones, transforming growth factor \u03b2 (TGF-\u03b2) and interleukin 23 (IL-23) in patients with Hashimoto\u2019s Thyroiditis","volume":"8","author":"Tajmiri","year":"2016","journal-title":"Eur J Integr Med"},{"key":"B31","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1179\/1476830514Y.0000000144","article-title":"The effects of Nigella sativa extract on hypothyroidism-associated learning and memory impairment during neonatal and juvenile growth in rats","volume":"20","author":"Beheshti","year":"2017","journal-title":"Nutr Neurosci"},{"key":"B32","doi-asserted-by":"publisher","first-page":"166","DOI":"10.4103\/2277-9175.221860","article-title":"The Effects of Hydroalcoholic Extract of Nigella sativa Seeds on Serum Estradiol and Prolactin Levels and obstetric Criteria due to Hypothyroidism in Rat","volume":"6","author":"Pakdel","year":"2017","journal-title":"Adv BioMed Res"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1080\/14767058.2018.1500540","article-title":"Administration of Nigella sativa during neonatal and juvenile growth period improved liver function of propylthiouracil-induced hypothyroid rats","volume":"33","author":"Hosseini","year":"2020","journal-title":"J Maternal-Fetal Neonatal Med"},{"key":"B34","doi-asserted-by":"publisher","first-page":"e13801","DOI":"10.1111\/JFBC.13801","article-title":"The positive effect of black seed (Nigella sativa L.) essential oil on thyroid hormones in rats with hypothyroidism and hyperthyroidism","volume":"46","author":"Avci","year":"2022","journal-title":"J Food Biochem"},{"key":"B35","doi-asserted-by":"crossref","DOI":"10.1016\/B978-0-12-824462-3.00001-9","article-title":"Therapeutic effects of Nigella sativa on hormonal dysfunctions","volume-title":"Black seeds (Nigella sativa): pharmacological and therapeutic applications","author":"Wani","year":"2022"},{"key":"B36","doi-asserted-by":"publisher","first-page":"103","DOI":"10.35516\/JJPS.V16I1.1072","article-title":"Comparison between the efficacy of nigella sativa aqueous extract and its oil on methimazole-induced hypothyroidism in albino mice","volume":"16","author":"Hassan","year":"2023","journal-title":"Jordan J Pharm Sci"},{"key":"B37","doi-asserted-by":"publisher","first-page":"e10665","DOI":"10.1016\/j.heliyon.2022.e10665","article-title":"Medicinal plants\u2019 proposed nanocomposites for the management of endocrine disorders","volume":"8","author":"Al Zarzour","year":"2022","journal-title":"Heliyon"},{"key":"B38","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.jsps.2020.12.004","article-title":"Ethnopharmacological study of herbal remedies used for the management of thyroid disorders in Algeria","volume":"29","author":"Ta\u00efbi","year":"2021","journal-title":"Saudi Pharm J"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1173855","article-title":"An insight into novel therapeutic potentials of taxifolin","volume":"14","author":"Liu","year":"2023","journal-title":"Front Pharmacol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.8b00760","article-title":"Polypharmacology by design: A medicinal chemist\u2019s perspective on multitargeting compounds","volume":"62","author":"Proschak","year":"2019","journal-title":"J Med Chem"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-025-04604-y","article-title":"Natural product-based interventions for thyroid disorders: mechanisms and applications","author":"El-Akad","year":"2025","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-018-22631-z","article-title":"IMPPAT: A curated database of Indian Medicinal Plants, Phytochemistry and Therapeutics","volume":"8","author":"Mohanraj","year":"2018","journal-title":"Sci Rep"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.3c00156","article-title":"IMPPAT 2.0: an enhanced and expanded phytochemical atlas of Indian medicinal plants","volume":"8","author":"Vivek-Ananth","year":"2023","journal-title":"ACS Omega"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.imu.2021.100734","article-title":"Molecular modelling and de novo fragment-based design of potential inhibitors of beta-tubulin gene of Necator americanus from natural products","volume":"26","author":"Agyapong","year":"2021","journal-title":"Inform Med Unlocked"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1021\/jm021080f","article-title":"Thyroid receptor ligands. 1. Agonist Ligands Selective for the Thyroid Receptor \u03b2 1","volume":"46","author":"Ye","year":"2003","journal-title":"J Med Chem"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-022-00646-6","article-title":"Structural insights into thyrotropin-releasing hormone receptor activation by an endogenous peptide agonist or its orally administered analogue","volume":"32","author":"Yang","year":"2022","journal-title":"Cell Res"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J Comput Chem"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1007\/s10822-010-9352-6","article-title":"Ligand docking and binding site analysis with PyMOL and Autodock\/Vina","volume":"24","author":"Seeliger","year":"2010","journal-title":"J Comput Aided Mol Des"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1093\/NAR\/GKV315","article-title":"PLIP: Fully automated protein-ligand interaction profiler","volume":"43","author":"Salentin","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae236","article-title":"ADMETlab 3.0: an updated comprehensive online ADMET prediction platform enhanced with broader coverage, improved performance, API functionality and decision support","volume":"52","author":"Fu","year":"2024","journal-title":"Nucleic Acids Res"},{"key":"B51","first-page":"529","article-title":"Uvarinol and Dichamanetin Derived from Uvaria chamae as Potential Dual-Site Inhibitors Against PBP2a in Methicillin Resistant Staphylococcus aureus : An In Silico Study","volume-title":"Pharmaceuticals","author":"Agbebi","year":"2025"},{"key":"B52","doi-asserted-by":"crossref","DOI":"10.1109\/SC.2006.54","article-title":"Scalable algorithms for molecular dynamics simulations on commodity clusters","author":"Bowers","year":"2006"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.8b01026","article-title":"OPLS3e: extending force field coverage for drug-like small molecules","volume":"15","author":"Roos","year":"2019","journal-title":"J Chem Theory Comput"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1126\/science.288.5473.1982a","article-title":"Origin update","volume":"288","author":"Mitchell","year":"2000","journal-title":"Sci (1979)"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1021\/AR000033J","article-title":"Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models","volume":"33","author":"Kollman","year":"2000","journal-title":"Acc Chem Res"},{"key":"B56","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1021\/CI100275A","article-title":"Assessing the performance of the MM\/PBSA and MM\/GBSA methods. 1. The accuracy of binding free energy calculations based on molecular dynamics simulations","volume":"51","author":"Hou","year":"2010","journal-title":"J Chem Inf Model"},{"key":"B57","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1517\/17460441.2015.1032936","article-title":"The MM\/PBSA and MM\/GBSA methods to estimate ligand-binding affinities","volume":"10","author":"Genheden","year":"2015","journal-title":"Expert Opin Drug Discov"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1021\/ACS.CHEMREV.9B00055","article-title":"End-point binding free energy calculation with MM\/PBSA and MM\/GBSA: strategies and applications in drug design","volume":"119","author":"Wang","year":"2019","journal-title":"Chem Rev"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.2174\/1389557523666230901152257\/CITE\/REFWORKS","article-title":"The power of molecular dynamics simulations and their applications to discover cysteine protease inhibitors","volume":"24","author":"dos Santos Nascimento","year":"2023","journal-title":"Mini-Reviews Medicinal Chem"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.3390\/METABO13101090","article-title":"Marine-derived compounds for CDK5 inhibition in cancer: integrating multi-stage virtual screening, MM\/GBSA analysis and molecular dynamics investigations","volume":"13","author":"Shoaib","year":"2023","journal-title":"Metabolites"},{"key":"B61","doi-asserted-by":"publisher","first-page":"5752","DOI":"10.3390\/molecules28155752","article-title":"Profiling the Antidiabetic Potential of Compounds Identified from Fractionated Extracts of Entada africana toward Glucokinase Stimulation : Computational Insight","volume":"28","author":"Onikanni","year":"2023","journal-title":"Molecules (Basel, Switzerland)"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.7326\/M15-1799","article-title":"The history and future of treatment of hypothyroidism","volume":"164","author":"McAninch","year":"2016","journal-title":"Ann Intern Med"},{"key":"B63","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jtice.2014.11.009","article-title":"Structural analysis of selective agonists of thyroid hormone receptor \u03b2 using 3D-QSAR and molecular docking","volume":"49","author":"Wang","year":"2015","journal-title":"J Taiwan Inst Chem Eng"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.3844\/ajisp.2008.33.42","article-title":"Hydrophobic, polar and hydrogen bonding based drug-receptor interaction of tetrahydroimidazobenzodiazepinones","volume":"4","author":"Sahu","year":"2008","journal-title":"American Journal of Immunology"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/J.TALANTA.2012.04.045","article-title":"Determination of n-octanol\/water partition coefficients of weak ionizable solutes by RP-HPLC with neutral model compounds","volume":"97","author":"Han","year":"2012","journal-title":"Talanta"},{"key":"B66","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.toxlet.2012.09.013","article-title":"Potential of the octanol\u2013water partition coefficient (logP) to predict the dermal penetration behaviour of amphiphilic compounds in aqueous solutions","volume":"215","author":"Korinth","year":"2012","journal-title":"Toxicol Lett"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.3390\/encyclopedia3020035","article-title":"Molecular filters in medicinal chemistry","volume":"3","author":"Kralj","year":"2023","journal-title":"Encyclopedia"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.46793\/CHEMN3.1.171I","article-title":"Lipinski\u2019s rule of five, famous extensions and famous exceptions","volume":"3","author":"Ivanovi\u0107","year":"2020","journal-title":"Chemia Naissensis"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/bs.apha.2025.01.007","article-title":"Molecular dynamics simulations: Insights into protein and protein ligand interactions","volume":"103","author":"Grewal","year":"2025","journal-title":"Advances in pharmacology (San Diego, Calif.)"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2021.1944909","article-title":"In silico screening of phytopolyphenolics for the identification of bioactive compounds as novel protease inhibitors effective against SARS-CoV-2","volume":"40","author":"Rudrapal","year":"2022","journal-title":"J Biomol Struct Dyn"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1727415\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T11:27:38Z","timestamp":1771932458000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1727415\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,16]]},"references-count":70,"alternative-id":["10.3389\/fendo.2026.1727415"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1727415","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,16]]},"article-number":"1727415"}}