{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T05:14:10Z","timestamp":1787289250362,"version":"build-2736575974"},"reference-count":39,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T00:00:00Z","timestamp":1664409600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Informatics"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A deep in silico investigation of various microsomal prostaglandin E<jats:sub>2<\/jats:sub> synthase\u20101 (mPGES\u20101) protein systems is here reported using molecular dynamics (MD) simulations. Firstly, eight different proteins models (Models A\u2212H) were built, starting from the active enzyme trimer system (Model A), namely that bound to three glutathione (GSH) cofactor molecules, and then gradually removing the GSHs (Models B\u2212H), simulating each of them for 100\u2005ns in explicit solvent. The analysis of the obtained data disclosed the structural role of GSH in the chemical architecture of mPGES\u20101 enzyme, thus suggesting the unlikely displacement of this cofactor, in accordance with experimentally determined protein structures co\u2010complexed with small molecule inhibitors. Afterwards, Model A was submitted to microsecond\u2010scale molecular dynamics simulation (total simulation time=10 \u03bcs), in order to shed light about the dynamical behaviour of this enzyme at atomic level and to obtain further structural features and protein function information. We confirmed the structural stability of the enzyme machinery, observing a conformational rigidity of the protein, with a backbone RMSD of \u223c3\u2005\u00c5 along the simulation time, and highlighting the strong active contribution of GSH molecules due to their active role in packing the protein chains through a tight binding at monomer interfaces. Furthermore, the focused analysis on R73 residue disclosed its role in solvent exchange events, probably excluding its function as route for GSH to enter towards the endoplasmic reticulum membrane, in line with the recently reported function of cap domain residues F44\u2010D66 as gatekeeper for GSH entrance into catalytic site.<\/jats:p>","DOI":"10.1002\/minf.202200140","type":"journal-article","created":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T02:18:28Z","timestamp":1662689908000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Extensive Molecular Dynamics Simulations Disclosed the Stability of mPGES\u20101 Enzyme and the Structural Role of Glutathione (GSH) Cofactor"],"prefix":"10.1002","volume":"41","author":[{"given":"Simone","family":"Di Micco","sequence":"first","affiliation":[{"name":"European Biomedical Research Institute of Salerno (EBRIS)  via Salvatore De Renzi 50 84125 Salerno Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluigi","family":"Lauro","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia University degli Studi di Salerno, via Giovanni Paolo II 132  84084 Fisciano (SA) Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1788-5170","authenticated-orcid":false,"given":"Giuseppe","family":"Bifulco","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia University degli Studi di Salerno, via Giovanni Paolo II 132  84084 Fisciano (SA) Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2019.03.003"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2004.047100"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-016-5087-x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.35.5.675"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2015.06.022"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2011.4408"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M400199200"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.20286"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2010.02.006"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b01750"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.7b01806"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1218504110"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2020.129800"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2017.10.039"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2021.676631"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20110977"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10822-013-9644-8"},{"key":"e_1_2_8_19_1","unstructured":"Maestro-Desmond Interoperability Tools version 4.2 Schr\u00f6dinger New York NY 2015."},{"key":"e_1_2_8_20_1","unstructured":"Desmond Molecular Dynamics System version 4.2 D.\u2005E. 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