{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:07:07Z","timestamp":1790014027627,"version":"4.0.1"},"update-to":[{"DOI":"10.12688\/f1000research.145391.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000}},{"DOI":"10.12688\/f1000research.145391.2","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000}}],"reference-count":58,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["2021-11506_F1"],"award-info":[{"award-number":["2021-11506_F1"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns5:p>Background The discovery of an ideal and effective therapy is urgently required for the treatment of Alzheimer\u2019s disease (AD). The main pathological hallmarks of Alzheimer\u2019s disease that appear before the clinical symptoms are neurofibrillary tangles, amyloid plaques, brain inflammation, and neuronal atrophy throughout the cerebral cortex and hippocampus. GSK-3\u03b2 (Glycogen Synthase Kinase-3\u03b2) is regarded as the most important and promising target for therapeutic use because GSK-3\u03b2 expression levels increase with age and are the most abundant and hyperactive in the brains of patients with AD. GSK-3\u03b2 activation or upregulation can contribute to neurodegeneration by promoting amyloid beta (A\u03b2) production and tau hyperphosphorylation. Whereas the underlying mechanism for abnormal production of GSK-3\u03b2 in AD brains remains unclear. Methods Maestro was used, which is Schrodinger, for our computational simulation studies. In the present work, different modules that were used in previous studies with a little modification, the modules such as Protein Preparation with the help of Protein Preparation Wizard, Ligand Preparation with the help of LigPrep, for ADME (Absorption, Distribution, Metabolism and Excretion) prediction Qikprop was used, for docking studies Glide module was used, Binding energy prediction the Prime was used and Molecular dynamic simulation (MDs) studies done using Desmond. Results Our focus is mainly on an <ns5:italic>in-silico<\/ns5:italic> approach, focusing on library generation; first draw an IMID2 (imidazo [1,5-a]pyridine-3-carboxamide) scaffold structure at Enamine and subjected it to a substructure search to target the receptor grid region (ATP-competitive site) of 6Y9R. They were then subjected to various screening processes. Finally, nine compounds were subjected to MDs studies. Conclusions Nine compounds showed good results with the most stable interactions. Among all the MD studies, the compound (Z3336252116) has shown good interaction and a good docking score. Further experiments and studies are required to confirm these results.<\/ns5:p>","DOI":"10.12688\/f1000research.145391.3","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T09:41:16Z","timestamp":1748338876000},"page":"773","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Molecular docking studies and molecular dynamic simulation analysis: To identify novel ATP-competitive inhibition of Glycogen synthase kinase-3\u03b2 for Alzheimer\u2019s disease"],"prefix":"10.12688","volume":"13","author":[{"given":"Suggala Ramya","family":"Shri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0508-1394","authenticated-orcid":false,"given":"Yogendra","family":"Nayak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2017-9533","authenticated-orcid":false,"given":"Sreedhara","family":"Ranganath Pai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2025,5,27]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"5-7","DOI":"10.29245\/2572.942X\/2018\/6.1227","article-title":"Novel Modality of GSK-3 Inhibition For Treating Neurodegeneration.","volume":"3","author":"I Rippin","year":"2018","journal-title":"J Neurol Neuromedicine."},{"key":"ref2","first-page":"1-22","article-title":"Enfermedad de Alzheimer: etiolog\u00eda, 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status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.159332.r302509, Qingchun Zhao, Shenyang Pharmaceutical University, Shenyang, 29 Jul 2024, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/13-773\/v1#referee-response-302509","order":0,"name":"referee-response-302509","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Sreedhara Ranganath Pai<\/b>; \n<i>Posted: 13 Aug 2024<\/i>; \n<b>Reviewer Comment 1:<\/b> In the abstract, the author describes the method as &quot;we have used different modules that were used in previous studies with a little modification&quot;, but in fact, the method used by the author is a routine application, and there is no prominent modification. \n<b>Response to comment 1<\/b>: We used Maestro, a graphical interface of Schrodinger, for our computational simulation studies. In the present work, we have used different modules such as Protein Preparation Wizard for Protein Preparation, LigPrep for Ligand Preparation, Qikprop for ADME (Absorption, Distribution, Metabolism and Excretion) prediction, Glide for docking studies, Prime for Binding energy prediction and Desmond for Molecular dynamic simulation studies used.  \n<b>Reviewer Comment 2<\/b>: In the introduction section, is there only one sentence to summarize the article? \n<b>Response to comment 2<\/b>: For better BBB permeation, the structure was finalized based on a wet lab. So, based on this literature search, we have selected core imidazole scaffold for our study, and from that core imidazole scaffold, we have drawn sub-structures in the enamine database. Then docking studies were done on the compounds and subjected to ADME (Qikprop). A molecular dynamic simulation study was conducted on nine compounds.  \n<b>Reviewer Comment 3<\/b>: The content of the whole study is simple, the innovation is poor, and the workload is less, which is not enough to support a research article. Therefore, it is hoped that the author can modify some contents of the article and add some follow-up experiments to make the article more comprehensive. \n<b>Response to comment 3<\/b>: The reviewer's comment is completely one-sided. We regret to answer this comment, and we completely disagree with the reviewer's suggestion, as this work took 18 months from the conceptualization of the idea. This work is computational modelling, and our objectives are clear, and in our view, the data generated is sufficient to make the conclusion.","URL":"https:\/\/f1000research.com\/articles\/13-773\/v3#referee-comment-12214","order":1,"name":"referee-comment-12214","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.159332.r302510, Jigna Samir Shah, Nirma University, Ahmedabad, Gujarat, 13 Sep 2024, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/13-773\/v1#referee-response-302510","order":2,"name":"referee-response-302510","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.170347.r318530, Sachchida Rai, Payal Singh, Centre of Experimental Medicine and Surgery (CEMS), Institute of Medical Sciences (IMS), Banaras Hindu University, Varanasi, Uttar Pradesh, 221005, 28 Sep 2024, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/13-773\/v2#referee-response-318530","order":3,"name":"referee-response-318530","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.159332.r302514, Shvetank Bhatt, Dr. Vishwanath Karad MIT World Peace University, Pune, Maharashtra, 10 Oct 2024, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/13-773\/v1#referee-response-302514","order":4,"name":"referee-response-302514","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"Indian Council of Medical Research (ICMR), New Delhi, India, for ICMR-SRF (#2021-11506_F1) to Suggala Ramya Shri. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":5,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}