Suggala Ramya Shri, Yogendra Nayak, Sreedhara Ranganath Pai
{"title":"分子对接研究和分子动态模拟分析:确定治疗阿尔茨海默病的糖原合酶激酶-3β的新型 ATP 竞争性抑制剂","authors":"Suggala Ramya Shri, Yogendra Nayak, Sreedhara Ranganath Pai","doi":"10.12688/f1000research.145391.1","DOIUrl":null,"url":null,"abstract":"Background The discovery of an ideal and effective therapy is urgently required for the treatment of Alzheimer’s disease. The main pathological hallmarks of Alzheimer’s disease that appear before the clinical symptoms are neurofibrillary tangles, amyloid plaques, brain inflammation, and neuronal atrophy throughout the cerebral cortex and hippocampus. GSK-3β (Glycogen Synthase Kinase-3β) is regarded as the most important and promising target for therapeutic use because GSK-3β expression levels increase with age and are the most abundant and hyperactive in the brains of patients with Alzheimer’s disease. Methods We used Maestro, which is Schrodinger, for our computational simulation studies. In the present work, we have used 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 we used Qikprop, Docking studies we used Glide module, Binding energy prediction we used Prime and Molecular dynamic simulation studies by Desmond Results Our focus is mainly on an in-silico approach, focusing on library generation; we first drew an imidazo [1,5-a]pyridine-3-carboxamide (IMID 2) 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, we selected nine compounds and subjected them to molecular dynamic simulation studies. Conclusions Nine compounds showed good results with the most stable interactions. Further experiments and studies are required to confirm these results.","PeriodicalId":12260,"journal":{"name":"F1000Research","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Molecular docking studies and molecular dynamic simulation analysis: To identify novel ATP-competitive inhibition of Glycogen synthase kinase-3β for Alzheimer’s disease\",\"authors\":\"Suggala Ramya Shri, Yogendra Nayak, Sreedhara Ranganath Pai\",\"doi\":\"10.12688/f1000research.145391.1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Background The discovery of an ideal and effective therapy is urgently required for the treatment of Alzheimer’s disease. The main pathological hallmarks of Alzheimer’s disease that appear before the clinical symptoms are neurofibrillary tangles, amyloid plaques, brain inflammation, and neuronal atrophy throughout the cerebral cortex and hippocampus. GSK-3β (Glycogen Synthase Kinase-3β) is regarded as the most important and promising target for therapeutic use because GSK-3β expression levels increase with age and are the most abundant and hyperactive in the brains of patients with Alzheimer’s disease. Methods We used Maestro, which is Schrodinger, for our computational simulation studies. In the present work, we have used 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 we used Qikprop, Docking studies we used Glide module, Binding energy prediction we used Prime and Molecular dynamic simulation studies by Desmond Results Our focus is mainly on an in-silico approach, focusing on library generation; we first drew an imidazo [1,5-a]pyridine-3-carboxamide (IMID 2) 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, we selected nine compounds and subjected them to molecular dynamic simulation studies. Conclusions Nine compounds showed good results with the most stable interactions. Further experiments and studies are required to confirm these results.\",\"PeriodicalId\":12260,\"journal\":{\"name\":\"F1000Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-07-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"F1000Research\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.12688/f1000research.145391.1\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"Pharmacology, Toxicology and Pharmaceutics\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"F1000Research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.12688/f1000research.145391.1","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Pharmacology, Toxicology and Pharmaceutics","Score":null,"Total":0}
Molecular docking studies and molecular dynamic simulation analysis: To identify novel ATP-competitive inhibition of Glycogen synthase kinase-3β for Alzheimer’s disease
Background The discovery of an ideal and effective therapy is urgently required for the treatment of Alzheimer’s disease. The main pathological hallmarks of Alzheimer’s disease that appear before the clinical symptoms are neurofibrillary tangles, amyloid plaques, brain inflammation, and neuronal atrophy throughout the cerebral cortex and hippocampus. GSK-3β (Glycogen Synthase Kinase-3β) is regarded as the most important and promising target for therapeutic use because GSK-3β expression levels increase with age and are the most abundant and hyperactive in the brains of patients with Alzheimer’s disease. Methods We used Maestro, which is Schrodinger, for our computational simulation studies. In the present work, we have used 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 we used Qikprop, Docking studies we used Glide module, Binding energy prediction we used Prime and Molecular dynamic simulation studies by Desmond Results Our focus is mainly on an in-silico approach, focusing on library generation; we first drew an imidazo [1,5-a]pyridine-3-carboxamide (IMID 2) 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, we selected nine compounds and subjected them to molecular dynamic simulation studies. Conclusions Nine compounds showed good results with the most stable interactions. Further experiments and studies are required to confirm these results.
F1000ResearchPharmacology, Toxicology and Pharmaceutics-Pharmacology, Toxicology and Pharmaceutics (all)
CiteScore
5.00
自引率
0.00%
发文量
1646
审稿时长
1 weeks
期刊介绍:
F1000Research publishes articles and other research outputs reporting basic scientific, scholarly, translational and clinical research across the physical and life sciences, engineering, medicine, social sciences and humanities. F1000Research is a scholarly publication platform set up for the scientific, scholarly and medical research community; each article has at least one author who is a qualified researcher, scholar or clinician actively working in their speciality and who has made a key contribution to the article. Articles must be original (not duplications). All research is suitable irrespective of the perceived level of interest or novelty; we welcome confirmatory and negative results, as well as null studies. F1000Research publishes different type of research, including clinical trials, systematic reviews, software tools, method articles, and many others. Reviews and Opinion articles providing a balanced and comprehensive overview of the latest discoveries in a particular field, or presenting a personal perspective on recent developments, are also welcome. See the full list of article types we accept for more information.