{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:14:05Z","timestamp":1772118845520,"version":"3.50.1"},"reference-count":38,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T00:00:00Z","timestamp":1745366400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1\u2010HD105944"],"award-info":[{"award-number":["RO1\u2010HD105944"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1 HD114311"],"award-info":[{"award-number":["RO1 HD114311"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21 HD107579"],"award-info":[{"award-number":["R21 HD107579"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006710","name":"Wayne State University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteins"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The interaction between meiosis\u2010expressed gene 1 (MEIG1) and Parkin co\u2010regulated gene (PACRG) is a critical determinant of spermiogenesis, the process by which round spermatids mature into functional spermatozoa. Disruption of the MEIG1\u2010PACRG complex can impair sperm development, highlighting its potential as a therapeutic target for addressing male infertility or for the development of non\u2010hormonal contraceptive methods. This study used virtual screening, molecular docking, and molecular dynamics (MD) simulations to identify small molecule inhibitors targeting the MEIG1\u2010PACRG interface. MD simulations provided representative protein conformations, which were used to virtually screen a library of 821\u2009438 compounds, resulting in 48 high\u2010ranking candidates for each protein. PACRG emerged as a favorable target due to its flexible binding pockets and better docking scores compared to MEIG1. Key binding residues with compounds included W50, Y68, N70, and E74 on MEIG1, and K93, W96, E101, and H137 on PACRG. MD simulations revealed that compound stability in MEIG1 complexes is primarily maintained by hydrogen bonding with E74 and \u03c0\u2010\u03c0 stacking interactions with W50 and Y68. In PACRG complexes, compound stabilization is facilitated by hydrogen bonding with E101 and \u03c0\u2010\u03c0 interactions involving W96 and H137. These findings highlight distinct molecular determinants of ligand binding for each protein. Our work provides mechanistic insights and identifies promising compounds for further experimental validation, establishing a foundation for developing MEIG1\u2010PACRG interaction inhibitors as male contraceptives.<\/jats:p>","DOI":"10.1002\/prot.26829","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T06:45:46Z","timestamp":1745390746000},"page":"1586-1602","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["In Silico Discovery of Potential Inhibitors Targeting the\n                    <scp>MEIG1<\/scp>\n                    \u2010\n                    <scp>PACRG<\/scp>\n                    Complex for Male Contraceptive Development"],"prefix":"10.1002","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1524-2489","authenticated-orcid":false,"given":"Timothy","family":"Hasse","sequence":"first","affiliation":[{"name":"Department of Physics and Astronomy Wayne State University  Detroit Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhibing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Physiology Wayne State University School of Medicine  Detroit Michigan USA"},{"name":"Department of Obstetrics and Gynecology Wayne State University  Detroit Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3257-6170","authenticated-orcid":false,"given":"Yu\u2010ming M.","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Physics and Astronomy Wayne State University  Detroit Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,4,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1210\/rp.57.1.103"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0012\u20101606(75)90411\u2010x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1530\/REP\u201015\u20100310"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.119834"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.101312"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep18278"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2016.344"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/ct300418h"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2021.01.001"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2008.02.081"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02659"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.26449"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521\u20103773(19990115)38:1\/2<236::AID\u2010ANIE236>3.0.CO;2\u2010M"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.softx.2015.06.001"},{"key":"e_1_2_9_16_1","unstructured":"Schr\u00f6dinger Release 2021\u20103: Glide \u201cGlide Schr\u00f6dinger \u201d(2021)."},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm0306430"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm030644s"},{"key":"e_1_2_9_19_1","unstructured":"ChemBridge \u201cCORE Library \u201dhttps:\/\/www.chembridge.com\/screening_libraries\/core_library\/."},{"key":"e_1_2_9_20_1","unstructured":"Schr\u00f6dinger Release 2021\u20133 \u201cLigPrep \u201d(2021)."},{"key":"e_1_2_9_21_1","unstructured":"Schr\u00f6dinger Release 2021\u20133 \u201cProtein Preparation Wizard \u201d(2021)."},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10822\u2010013\u20109644\u20108"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja9621760"},{"key":"e_1_2_9_24_1","unstructured":"Schr\u00f6dinger Release 2021\u20133 \u201cMaestro \u201d(2021)."},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0263\u20107855(96)00018\u20105"},{"key":"e_1_2_9_26_1","volume-title":"Amber 2020","author":"Case D. 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