{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T20:08:11Z","timestamp":1787170091640,"version":"build-2736575974"},"reference-count":13,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2008,6,30]],"date-time":"2008-06-30T00:00:00Z","timestamp":1214784000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Estrogen receptors (ER) are known as nuclear receptors. They exist in the cytoplasm of human cells and serves as a DNA binding transcription factor that regulates gene expression. However the estrogen receptor also has additional functions independent of DNA binding. The human estrogen receptor comes in two forms, alpha and beta. This work focuses on the alpha form of the estrogen receptor. The ER\u03b1 is found in breast cancer cells, ovarian stroma cells, endometrium, and the hypothalamus. It has been suggested that exposure to DDE, a metabolite of DDT, and other pesticides causes conformational changes in the estrogen receptor. Before examining these factors, this work examines the protein unfolding from the antagonist form found in the 3ERT PDB crystal structure. The 3ERT PDB crystal structure has the estrogen receptor bound to the cancer drug 4-hydroxytamoxifen. The 4-hydroxytamoxifen ligand was extracted before the simulation, resulting in new conformational freedom due to absence of van der Waals contacts between the ligand and the receptor. The conformational changes that result expose the binding clef of the co peptide beside Helix 12 of the receptor forming an apo conformation. Two key conformations in the loops at either end of the H12 are produced resulting in the antagonist to apo conformation transformation. The results were produced over a 42ns Molecular Dynamics simulation using the AMBER FF99SB force field.<\/jats:p>","DOI":"10.3390\/ijerph5020111","type":"journal-article","created":{"date-parts":[[2008,12,1]],"date-time":"2008-12-01T09:42:49Z","timestamp":1228124569000},"page":"111-114","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Preliminary Molecular Dynamic Simulations of the Estrogen Receptor Alpha Ligand Binding Domain from Antagonist to Apo"],"prefix":"10.3390","volume":"5","author":[{"given":"T. Dwight","family":"McGee","sequence":"first","affiliation":[{"name":"Department of Chemistry, Florida A & M University, Tallahassee, FL, 32307, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse","family":"Edwards","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Florida A & M University, Tallahassee, FL, 32307, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian E.","family":"Roitberg","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Quantum Theory Project, University of Florida, Gainesville, FL 32608, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2008,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.febslet.2004.12.025","article-title":"A novel pesticide-induced conformational state of the oestrogen receptor ligand-binding domain, detected by conformation-specific peptide binding","volume":"579","author":"Sumbayev","year":"2005","journal-title":"FEBS Lett"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/S0092-8674(00)81717-1","article-title":"The structural basis of estrogen receptor\/coactivator recognition and the antagonism of this interaction by tamoxifen","volume":"95","author":"Shiau","year":"1998","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5998","DOI":"10.1073\/pnas.95.11.5998","article-title":"Crystallographic comparison of the estrogen and pogesterone receptor\u2019s ligand binding domain","volume":"95","author":"Tanenbaum","year":"1998","journal-title":"Proc Nat Acad Sci USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1021\/jm0309607","article-title":"Prediction of ligand binding affinity and orientation of xenoestrogens to the estrogen receptor by molecular dynamics simulations and the linear interaction energy method","volume":"47","author":"Laak","year":"2004","journal-title":"J Med Chem"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1152\/physrev.2001.81.4.1535","article-title":"Mechanisms of Estrogne action","volume":"81","author":"Nilsson","year":"2001","journal-title":"Physiol Rev"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/S0092-8674(02)00641-4","article-title":"Combinatorial control of gene expression by nuclear receptors and coregulators","volume":"108","author":"McKenna","year":"2002","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1021\/bi061656t","article-title":"Conformational dynamics of the Estrogen Receptor a: Moleulcar Dynamics Simulations of the Influence of Binding Site Structure on Protein Dynamics","volume":"46","author":"Celik","year":"2007","journal-title":"Biochemistry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1002\/jcc.20290","article-title":"The Amber biomolecular simulation programs","volume":"26","author":"Case","year":"2005","journal-title":"J Comput Chem"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0010-4655(95)00041-D","article-title":"AMBER, a computer program for applying molecular mechanics, normal mode analysis, molecular dynamics and free energy calculations to elucidate the structures and energies of molecules","volume":"91","author":"Pearlman","year":"1995","journal-title":"Comp Phys Commun"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1021\/jp992433y","article-title":"Understanding modern molecular dynamics: Techniques and applications","volume":"104","author":"Tuckerman","year":"2000","journal-title":"J Phys Chem B"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4177","DOI":"10.1063\/1.467468","article-title":"Constant-pressure molecular dynamic algorithms","volume":"101","author":"Martyna","year":"1994","journal-title":"J Chem Phys"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3684","DOI":"10.1063\/1.448118","article-title":"Molecular dynamics with coupling to an external bath","volume":"81","author":"Berendsen","year":"1984","journal-title":"J Chem Phys"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD - 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