{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T04:39:55Z","timestamp":1784349595022,"version":"3.55.0"},"reference-count":30,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T00:00:00Z","timestamp":1721865600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100023674","name":"Deanship of Scientific Research, King Khalid University","doi-asserted-by":"publisher","award":["RGP2\/355\/44."],"award-info":[{"award-number":["RGP2\/355\/44."]}],"id":[{"id":"10.13039\/501100023674","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Alzheimer\u2019s Disease (AD) is the prevailing type of neurodegenerative illness, characterised by the accumulation of amyloid beta plaques. The symptoms associated with AD are memory loss, emotional variability, and a decline in cognitive functioning. To date, the pharmaceuticals currently accessible in the marketplace are limited to symptom management. According to several research, antidepressants have demonstrated potential efficacy in the management of AD. In this particular investigation, a total of 24 anti-depressant medications were selected as ligands, while the Microtubule Affinity Receptor Kinase 4 (MARK4) protein was chosen as the focal point of our study. The selection of MARK4 was based on its known involvement in the advancement of AD and other types of malignancies, rendering it a highly prospective target for therapeutic interventions. The initial step involved doing ADMET analysis, which was subsequently followed by molecular docking of 24 drugs. This was succeeded by molecular dynamics simulation and molecular mechanics generalised Born surface area (MMGBSA) calculations. Upon conducting molecular docking experiments, it has been determined that the binding affinities observed fall within the range of -5.5 kcal\/mol to -9.0 kcal\/mol. In this study, we selected six anti-depressant compounds (CID ID \u2010 4184, 2771, 4205, 5533, 4543, and 2160) based on their binding affinities, which were determined to be -9.0, -8.7, -8.4, -8.3, -8.2, and -8.2, respectively. Molecular dynamics simulations were conducted for all six drugs, with donepezil serving as the control drug. Various analyses were performed, including basic analysis and post-trajectory analysis such as free energy landscape (FEL), polarizable continuum model (PCM), and MMGBSA calculations. Based on the findings from molecular dynamics simulations and the MMGBSA analysis, it can be inferred that citalopram and mirtazapine exhibit considerable potential as anti-depressant agents. Consequently, these compounds warrant further investigation through <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> investigations in the context of treating AD.<\/jats:p>","DOI":"10.1371\/journal.pone.0301179","type":"journal-article","created":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T17:40:49Z","timestamp":1721929249000},"page":"e0301179","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploring the most promising anti \u2010 Depressant drug targeting Microtubule Affinity Receptor Kinase 4 involved in Alzheimer\u2019s Disease through molecular docking and molecular dynamics simulation"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0796-5238","authenticated-orcid":true,"given":"S. Rehan","family":"Ahmad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md.","family":"Zeyaullah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah M.","family":"AlShahrani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Suhail","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1676-8092","authenticated-orcid":true,"given":"Khursheed","family":"Muzammil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faheem","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Dawria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Mohieldin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haroon","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9560-2607","authenticated-orcid":true,"given":"Abdelrhman A. 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Faizan Ahmad Ahmad","year":"2022","journal-title":"Aging Medicine"},{"key":"pone.0301179.ref003","first-page":"1","volume":"00","author":"Ahmad Faizan","year":"2022","journal-title":"Punya Sachdeva Critical appraisal on mitochondrial dysfunction in Alzheimer\u2019s disease Aging Medicine"},{"issue":"4","key":"pone.0301179.ref004","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.3233\/JAD-160780","article-title":"Risk Factors and Pathological Substrates Associated with Agitation\/Aggression in Alzheimer\u2019s Disease: A Preliminary Study using NACC Data","volume":"55","author":"S Sennik","year":"2017","journal-title":"J Alzheimers Dis"},{"key":"pone.0301179.ref005","first-page":"1","volume":"00","author":"Ahmad Faizan","year":"2022","journal-title":"Punya Sachdeva A consolidated review on stem cell therapy for treatment and management of Alzheimer\u2019s disease Aging Medicine"},{"issue":"1","key":"pone.0301179.ref006","article-title":"Cholinesterase inhibitors for Alzheimer\u2019s disease","volume":"2006","author":"J. 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