{"title":"研究胆固醇对gp41驱动的HIV膜融合的影响","authors":"Jatin Soni, and , Taraknath Mandal*, ","doi":"10.1021/acs.jctc.5c00962","DOIUrl":null,"url":null,"abstract":"<p >Membrane fusion is a critical step in HIV infection, allowing the virus envelope to merge with the host cell membrane and deliver genetic material. Cholesterol is believed to play a pivotal role in HIV fusion; however, the specific mechanism by which it facilitates membrane fusion remains poorly understood. Our molecular dynamics simulation study elucidates the dual role of cholesterol: it promotes GP41 aggregation by reducing the dimerization free energy and enhances the strengths of the protein-induced membrane curvatures. The free energy calculations reveal that by enhancing membrane curvatures, cholesterol significantly reduces the energy barriers and stabilizes the fusion intermediates. These findings highlight cholesterol’s essential role in facilitating HIV entry and offer insights for potential antiviral strategies.</p>","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":"21 18","pages":"9164–9174"},"PeriodicalIF":5.5000,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Investigating the Impact of Cholesterol on GP41-Driven HIV Membrane Fusion\",\"authors\":\"Jatin Soni, and , Taraknath Mandal*, \",\"doi\":\"10.1021/acs.jctc.5c00962\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Membrane fusion is a critical step in HIV infection, allowing the virus envelope to merge with the host cell membrane and deliver genetic material. Cholesterol is believed to play a pivotal role in HIV fusion; however, the specific mechanism by which it facilitates membrane fusion remains poorly understood. Our molecular dynamics simulation study elucidates the dual role of cholesterol: it promotes GP41 aggregation by reducing the dimerization free energy and enhances the strengths of the protein-induced membrane curvatures. The free energy calculations reveal that by enhancing membrane curvatures, cholesterol significantly reduces the energy barriers and stabilizes the fusion intermediates. These findings highlight cholesterol’s essential role in facilitating HIV entry and offer insights for potential antiviral strategies.</p>\",\"PeriodicalId\":45,\"journal\":{\"name\":\"Journal of Chemical Theory and Computation\",\"volume\":\"21 18\",\"pages\":\"9164–9174\"},\"PeriodicalIF\":5.5000,\"publicationDate\":\"2025-08-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Chemical Theory and Computation\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acs.jctc.5c00962\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, PHYSICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Chemical Theory and Computation","FirstCategoryId":"92","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.jctc.5c00962","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}
Investigating the Impact of Cholesterol on GP41-Driven HIV Membrane Fusion
Membrane fusion is a critical step in HIV infection, allowing the virus envelope to merge with the host cell membrane and deliver genetic material. Cholesterol is believed to play a pivotal role in HIV fusion; however, the specific mechanism by which it facilitates membrane fusion remains poorly understood. Our molecular dynamics simulation study elucidates the dual role of cholesterol: it promotes GP41 aggregation by reducing the dimerization free energy and enhances the strengths of the protein-induced membrane curvatures. The free energy calculations reveal that by enhancing membrane curvatures, cholesterol significantly reduces the energy barriers and stabilizes the fusion intermediates. These findings highlight cholesterol’s essential role in facilitating HIV entry and offer insights for potential antiviral strategies.
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The Journal of Chemical Theory and Computation invites new and original contributions with the understanding that, if accepted, they will not be published elsewhere. Papers reporting new theories, methodology, and/or important applications in quantum electronic structure, molecular dynamics, and statistical mechanics are appropriate for submission to this Journal. Specific topics include advances in or applications of ab initio quantum mechanics, density functional theory, design and properties of new materials, surface science, Monte Carlo simulations, solvation models, QM/MM calculations, biomolecular structure prediction, and molecular dynamics in the broadest sense including gas-phase dynamics, ab initio dynamics, biomolecular dynamics, and protein folding. The Journal does not consider papers that are straightforward applications of known methods including DFT and molecular dynamics. The Journal favors submissions that include advances in theory or methodology with applications to compelling problems.
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