T-20 and T-1249 HIV fusion inhibitors’ structure and conformational behavior in solution: a molecular dynamics study
Autor(a) principal: | |
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Data de Publicação: | 2007 |
Outros Autores: | , |
Tipo de documento: | Artigo de conferência |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10174/1191 |
Resumo: | Fusion of the HIV envelope with the target cell membrane is a critical step of HIV entry into the target cell. Several peptides based on the C-region of HIV gp41 have been used in clinical trials as possible HIV fusion inhibitors. Among these are T-1249 and T-20 (also known as enfurvitide; see fig. 1). Despite recent works, a detailed molecular picture of the inhibitory mechanism of these molecules is still lacking. These peptides are usually depicted as α-helices by analogy with the structure of the sequence of the gp41 protein with which they are homologous. However, structures like these would not explain the ability that the two fusion inhibitors have to both become solvated by water and interact effectively with cell membranes. This led us to study the structure and conformational behavior of all these peptides. To this effect, extensive molecular dynamics simulations (total time 400 ns) with explicit solvent (SPC water) were carried out to investigate the structure and conformational behavior of T-1249 and T-20, as well as shorter homologous peptides CTP and 3f5 (see fig. 1), which show no inhibitory action. The monitored parameters include mean square displacement relative to the initial conformation (α-helix structures in all cases), secondary structure, solvent accessible surface and radius of gyration. We found that the studied peptides have no stable structure in solution in the time scale studied. Additionally, the solvent accessible area varies significantly during the simulation. Our findings suggest that these peptides may assume not only one but several possible sets of structures in solution, some of which more adequate to interact with the solvent, whereas others might be better suited to interact with cell membranes. |
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T-20 and T-1249 HIV fusion inhibitors’ structure and conformational behavior in solution: a molecular dynamics studyAIDSHIV fusion inhibitorenfurvitideT-20T-1249molecular dynamicsmolecular simulationsFusion of the HIV envelope with the target cell membrane is a critical step of HIV entry into the target cell. Several peptides based on the C-region of HIV gp41 have been used in clinical trials as possible HIV fusion inhibitors. Among these are T-1249 and T-20 (also known as enfurvitide; see fig. 1). Despite recent works, a detailed molecular picture of the inhibitory mechanism of these molecules is still lacking. These peptides are usually depicted as α-helices by analogy with the structure of the sequence of the gp41 protein with which they are homologous. However, structures like these would not explain the ability that the two fusion inhibitors have to both become solvated by water and interact effectively with cell membranes. This led us to study the structure and conformational behavior of all these peptides. To this effect, extensive molecular dynamics simulations (total time 400 ns) with explicit solvent (SPC water) were carried out to investigate the structure and conformational behavior of T-1249 and T-20, as well as shorter homologous peptides CTP and 3f5 (see fig. 1), which show no inhibitory action. The monitored parameters include mean square displacement relative to the initial conformation (α-helix structures in all cases), secondary structure, solvent accessible surface and radius of gyration. We found that the studied peptides have no stable structure in solution in the time scale studied. Additionally, the solvent accessible area varies significantly during the simulation. Our findings suggest that these peptides may assume not only one but several possible sets of structures in solution, some of which more adequate to interact with the solvent, whereas others might be better suited to interact with cell membranes.2008-06-03T10:36:06Z2008-06-032007-04-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObject167816 bytesapplication/pdfhttp://hdl.handle.net/10174/1191http://hdl.handle.net/10174/1191engLisbon, PortugalPoster apresentado na conferência "2nd workshop on biophysics of membrane-active peptides"naonaosimlivreammc@uevora.ptajpalace@uevora.ptjpcar@uevora.ptCanto, A. M. T. M.Palace Carvalho, A. J.Prates Ramalho, J. P.info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-01-03T18:36:55Zoai:dspace.uevora.pt:10174/1191Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T00:57:14.477674Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
T-20 and T-1249 HIV fusion inhibitors’ structure and conformational behavior in solution: a molecular dynamics study |
title |
T-20 and T-1249 HIV fusion inhibitors’ structure and conformational behavior in solution: a molecular dynamics study |
spellingShingle |
T-20 and T-1249 HIV fusion inhibitors’ structure and conformational behavior in solution: a molecular dynamics study Canto, A. M. T. M. AIDS HIV fusion inhibitor enfurvitide T-20 T-1249 molecular dynamics molecular simulations |
title_short |
T-20 and T-1249 HIV fusion inhibitors’ structure and conformational behavior in solution: a molecular dynamics study |
title_full |
T-20 and T-1249 HIV fusion inhibitors’ structure and conformational behavior in solution: a molecular dynamics study |
title_fullStr |
T-20 and T-1249 HIV fusion inhibitors’ structure and conformational behavior in solution: a molecular dynamics study |
title_full_unstemmed |
T-20 and T-1249 HIV fusion inhibitors’ structure and conformational behavior in solution: a molecular dynamics study |
title_sort |
T-20 and T-1249 HIV fusion inhibitors’ structure and conformational behavior in solution: a molecular dynamics study |
author |
Canto, A. M. T. M. |
author_facet |
Canto, A. M. T. M. Palace Carvalho, A. J. Prates Ramalho, J. P. |
author_role |
author |
author2 |
Palace Carvalho, A. J. Prates Ramalho, J. P. |
author2_role |
author author |
dc.contributor.author.fl_str_mv |
Canto, A. M. T. M. Palace Carvalho, A. J. Prates Ramalho, J. P. |
dc.subject.por.fl_str_mv |
AIDS HIV fusion inhibitor enfurvitide T-20 T-1249 molecular dynamics molecular simulations |
topic |
AIDS HIV fusion inhibitor enfurvitide T-20 T-1249 molecular dynamics molecular simulations |
description |
Fusion of the HIV envelope with the target cell membrane is a critical step of HIV entry into the target cell. Several peptides based on the C-region of HIV gp41 have been used in clinical trials as possible HIV fusion inhibitors. Among these are T-1249 and T-20 (also known as enfurvitide; see fig. 1). Despite recent works, a detailed molecular picture of the inhibitory mechanism of these molecules is still lacking. These peptides are usually depicted as α-helices by analogy with the structure of the sequence of the gp41 protein with which they are homologous. However, structures like these would not explain the ability that the two fusion inhibitors have to both become solvated by water and interact effectively with cell membranes. This led us to study the structure and conformational behavior of all these peptides. To this effect, extensive molecular dynamics simulations (total time 400 ns) with explicit solvent (SPC water) were carried out to investigate the structure and conformational behavior of T-1249 and T-20, as well as shorter homologous peptides CTP and 3f5 (see fig. 1), which show no inhibitory action. The monitored parameters include mean square displacement relative to the initial conformation (α-helix structures in all cases), secondary structure, solvent accessible surface and radius of gyration. We found that the studied peptides have no stable structure in solution in the time scale studied. Additionally, the solvent accessible area varies significantly during the simulation. Our findings suggest that these peptides may assume not only one but several possible sets of structures in solution, some of which more adequate to interact with the solvent, whereas others might be better suited to interact with cell membranes. |
publishDate |
2007 |
dc.date.none.fl_str_mv |
2007-04-01T00:00:00Z 2008-06-03T10:36:06Z 2008-06-03 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/conferenceObject |
format |
conferenceObject |
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publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10174/1191 http://hdl.handle.net/10174/1191 |
url |
http://hdl.handle.net/10174/1191 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Lisbon, Portugal Poster apresentado na conferência "2nd workshop on biophysics of membrane-active peptides" nao nao sim livre ammc@uevora.pt ajpalace@uevora.pt jpcar@uevora.pt |
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info:eu-repo/semantics/openAccess |
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openAccess |
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167816 bytes application/pdf |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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