B. Akshaya Devi, Dhananjay Jade, K. H Sreenithya, Michael A. Harrison, Shobana Sugumar
{"title":"针对幽门螺旋杆菌的外排泵抑制剂的虚拟筛选、对接和分子动力学研究","authors":"B. Akshaya Devi, Dhananjay Jade, K. H Sreenithya, Michael A. Harrison, Shobana Sugumar","doi":"10.1007/s11696-024-03719-5","DOIUrl":null,"url":null,"abstract":"<div><p><i>Helicobacter pylori</i> is a Gram-negative bacterium that infects the human gastrointestinal mucosa and is a significant human pathogen, affecting 50% of the world’s population. Multidrug Efflux Pump mepA from the MATE family of proteins acts as a potential efflux pump target in <i>Helicobacter pylori</i> which exports multiple drugs outside the <i>Helicobacter pylori</i> and consists of 417 amino acids. This study aimed to identify potential inhibitors of the multidrug efflux pump mepA in <i>Helicobacter pylori</i> using <i>in-silico</i> approaches that employed molecular docking, drug-likeness evaluation, density functional theory [DFT], molecular dynamics (MD) simulations, and free energy calculations to analyze, the interactions between phytochemicals compounds and mepA protein. The best compounds exhibiting the highest binding affinities toward mepA were selected among all the screened phytochemical compounds from the database. Overall, this research identified three promising natural compounds Hinokiflavone (− 10.9 kcal/mol), Ipomine (− 10.7 kcal/mol), and Lupinisoflavone M (− 10.5 kcal/mol) from 30 top compounds based on binding affinity score, which demonstrated remarkable binding affinities toward mepA through molecular docking, suggesting their potential to block the efflux pump and potentiate antibiotic action with the potential to inhibit the multidrug efflux pump mepA in <i>Helicobacter pylori</i>. Besides, we select one complex for 3 compounds for an analysis of DFT and calculate the stability of protein and protein–ligand complex by Molecular Dynamics simulation along with this we calculate the binding free energy for the complex’s protein for selected Lupinisoflavone M complex (− 98.948 kJ/mol). The study highlights the promising capacity of the selected compounds to inhibit the mepA efflux pump, potentially paving the way for developing novel therapeutic strategies against multidrug-resistant pathogens.</p><h3>Graphical abstract</h3>\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":513,"journal":{"name":"Chemical Papers","volume":"78 16","pages":"8889 - 8902"},"PeriodicalIF":2.2000,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Virtual screening, docking, molecular dynamics study of efflux pump inhibitors against Helicobacter pylori\",\"authors\":\"B. Akshaya Devi, Dhananjay Jade, K. H Sreenithya, Michael A. 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The best compounds exhibiting the highest binding affinities toward mepA were selected among all the screened phytochemical compounds from the database. Overall, this research identified three promising natural compounds Hinokiflavone (− 10.9 kcal/mol), Ipomine (− 10.7 kcal/mol), and Lupinisoflavone M (− 10.5 kcal/mol) from 30 top compounds based on binding affinity score, which demonstrated remarkable binding affinities toward mepA through molecular docking, suggesting their potential to block the efflux pump and potentiate antibiotic action with the potential to inhibit the multidrug efflux pump mepA in <i>Helicobacter pylori</i>. Besides, we select one complex for 3 compounds for an analysis of DFT and calculate the stability of protein and protein–ligand complex by Molecular Dynamics simulation along with this we calculate the binding free energy for the complex’s protein for selected Lupinisoflavone M complex (− 98.948 kJ/mol). The study highlights the promising capacity of the selected compounds to inhibit the mepA efflux pump, potentially paving the way for developing novel therapeutic strategies against multidrug-resistant pathogens.</p><h3>Graphical abstract</h3>\\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>\",\"PeriodicalId\":513,\"journal\":{\"name\":\"Chemical Papers\",\"volume\":\"78 16\",\"pages\":\"8889 - 8902\"},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2024-10-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Chemical Papers\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s11696-024-03719-5\",\"RegionNum\":4,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"Engineering\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chemical Papers","FirstCategoryId":"92","ListUrlMain":"https://link.springer.com/article/10.1007/s11696-024-03719-5","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Engineering","Score":null,"Total":0}
Virtual screening, docking, molecular dynamics study of efflux pump inhibitors against Helicobacter pylori
Helicobacter pylori is a Gram-negative bacterium that infects the human gastrointestinal mucosa and is a significant human pathogen, affecting 50% of the world’s population. Multidrug Efflux Pump mepA from the MATE family of proteins acts as a potential efflux pump target in Helicobacter pylori which exports multiple drugs outside the Helicobacter pylori and consists of 417 amino acids. This study aimed to identify potential inhibitors of the multidrug efflux pump mepA in Helicobacter pylori using in-silico approaches that employed molecular docking, drug-likeness evaluation, density functional theory [DFT], molecular dynamics (MD) simulations, and free energy calculations to analyze, the interactions between phytochemicals compounds and mepA protein. The best compounds exhibiting the highest binding affinities toward mepA were selected among all the screened phytochemical compounds from the database. Overall, this research identified three promising natural compounds Hinokiflavone (− 10.9 kcal/mol), Ipomine (− 10.7 kcal/mol), and Lupinisoflavone M (− 10.5 kcal/mol) from 30 top compounds based on binding affinity score, which demonstrated remarkable binding affinities toward mepA through molecular docking, suggesting their potential to block the efflux pump and potentiate antibiotic action with the potential to inhibit the multidrug efflux pump mepA in Helicobacter pylori. Besides, we select one complex for 3 compounds for an analysis of DFT and calculate the stability of protein and protein–ligand complex by Molecular Dynamics simulation along with this we calculate the binding free energy for the complex’s protein for selected Lupinisoflavone M complex (− 98.948 kJ/mol). The study highlights the promising capacity of the selected compounds to inhibit the mepA efflux pump, potentially paving the way for developing novel therapeutic strategies against multidrug-resistant pathogens.
Chemical PapersChemical Engineering-General Chemical Engineering
CiteScore
3.30
自引率
4.50%
发文量
590
期刊介绍:
Chemical Papers is a peer-reviewed, international journal devoted to basic and applied chemical research. It has a broad scope covering the chemical sciences, but favors interdisciplinary research and studies that bring chemistry together with other disciplines.