Molecular models of NS3 protease variants of the Hepatitis C virus
Autor(a) principal: | |
---|---|
Data de Publicação: | 2005 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1186/1472-6807-5-1 http://hdl.handle.net/11449/21342 |
Resumo: | Background: Hepatitis C virus (HCV) currently infects approximately three percent of the world population. In view of the lack of vaccines against HCV, there is an urgent need for an efficient treatment of the disease by an effective antiviral drug. Rational drug design has not been the primary way for discovering major therapeutics. Nevertheless, there are reports of success in the development of inhibitor using a structure-based approach. One of the possible targets for drug development against HCV is the NS3 protease variants. Based on the three-dimensional structure of these variants we expect to identify new NS3 protease inhibitors. In order to speed up the modeling process all NS3 protease variant models were generated in a Beowulf cluster. The potential of the structural bioinformatics for development of new antiviral drugs is discussed.Results: the atomic coordinates of crystallographic structure 1CU1 and 1DY9 were used as starting model for modeling of the NS3 protease variant structures. The NS3 protease variant structures are composed of six subdomains, which occur in sequence along the polypeptide chain. The protease domain exhibits the dual beta-barrel fold that is common among members of the chymotrypsin serine protease family. The helicase domain contains two structurally related beta-alpha-beta subdomains and a third subdomain of seven helices and three short beta strands. The latter domain is usually referred to as the helicase alpha-helical subdomain. The rmsd value of bond lengths and bond angles, the average G-factor and Verify 3D values are presented for NS3 protease variant structures.Conclusions: This project increases the certainty that homology modeling is an useful tool in structural biology and that it can be very valuable in annotating genome sequence information and contributing to structural and functional genomics from virus. The structural models will be used to guide future efforts in the structure-based drug design of a new generation of NS3 protease variants inhibitors. All models in the database are publicly accessible via our interactive website, providing us with large amount of structural models for use in protein-ligand docking analysis. |
id |
UNSP_41b5672ddab650c4e66a7463c1d64d70 |
---|---|
oai_identifier_str |
oai:repositorio.unesp.br:11449/21342 |
network_acronym_str |
UNSP |
network_name_str |
Repositório Institucional da UNESP |
repository_id_str |
2946 |
spelling |
Molecular models of NS3 protease variants of the Hepatitis C virusBackground: Hepatitis C virus (HCV) currently infects approximately three percent of the world population. In view of the lack of vaccines against HCV, there is an urgent need for an efficient treatment of the disease by an effective antiviral drug. Rational drug design has not been the primary way for discovering major therapeutics. Nevertheless, there are reports of success in the development of inhibitor using a structure-based approach. One of the possible targets for drug development against HCV is the NS3 protease variants. Based on the three-dimensional structure of these variants we expect to identify new NS3 protease inhibitors. In order to speed up the modeling process all NS3 protease variant models were generated in a Beowulf cluster. The potential of the structural bioinformatics for development of new antiviral drugs is discussed.Results: the atomic coordinates of crystallographic structure 1CU1 and 1DY9 were used as starting model for modeling of the NS3 protease variant structures. The NS3 protease variant structures are composed of six subdomains, which occur in sequence along the polypeptide chain. The protease domain exhibits the dual beta-barrel fold that is common among members of the chymotrypsin serine protease family. The helicase domain contains two structurally related beta-alpha-beta subdomains and a third subdomain of seven helices and three short beta strands. The latter domain is usually referred to as the helicase alpha-helical subdomain. The rmsd value of bond lengths and bond angles, the average G-factor and Verify 3D values are presented for NS3 protease variant structures.Conclusions: This project increases the certainty that homology modeling is an useful tool in structural biology and that it can be very valuable in annotating genome sequence information and contributing to structural and functional genomics from virus. The structural models will be used to guide future efforts in the structure-based drug design of a new generation of NS3 protease variants inhibitors. All models in the database are publicly accessible via our interactive website, providing us with large amount of structural models for use in protein-ligand docking analysis.UNESP, Dept Phys, IBILCE, Sao Jose do Rio Preto, SP, BrazilUSP, Dept Microbiol, Inst Biomed Sci, BR-09500900 São Paulo, BrazilAdolfo Lutz Inst, São Paulo, BrazilUNESP, Dept Biol, IBILCE, Sao Jose do Rio Preto, SP, BrazilInstituto Butantan, Ctr Appl Toxicol, São Paulo, BrazilUNESP, Dept Phys, IBILCE, Sao Jose do Rio Preto, SP, BrazilUNESP, Dept Biol, IBILCE, Sao Jose do Rio Preto, SP, BrazilBiomed Central Ltd.Universidade Estadual Paulista (Unesp)Universidade de São Paulo (USP)Instituto Adolfo Lutz (IAL)Instituto Butantanda Silveira, NJFArcuri, H. A.Bonalumi, C. E.de Souza, F. P.Mello, IMVGCRahal, Paula [UNESP]Pinho, JRRde Azevedo, W. F.2014-05-20T14:00:20Z2014-05-20T14:00:20Z2005-01-21info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article8application/pdfhttp://dx.doi.org/10.1186/1472-6807-5-1Bmc Structural Biology. London: Biomed Central Ltd., v. 5, 8 p., 2005.1471-2237http://hdl.handle.net/11449/2134210.1186/1472-6807-5-1WOS:000234256300001WOS000234256300001.pdf79910823626712120000-0001-5693-6148Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengBmc Structural Biologyinfo:eu-repo/semantics/openAccess2023-12-29T06:19:33Zoai:repositorio.unesp.br:11449/21342Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T21:35:54.865971Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Molecular models of NS3 protease variants of the Hepatitis C virus |
title |
Molecular models of NS3 protease variants of the Hepatitis C virus |
spellingShingle |
Molecular models of NS3 protease variants of the Hepatitis C virus da Silveira, NJF |
title_short |
Molecular models of NS3 protease variants of the Hepatitis C virus |
title_full |
Molecular models of NS3 protease variants of the Hepatitis C virus |
title_fullStr |
Molecular models of NS3 protease variants of the Hepatitis C virus |
title_full_unstemmed |
Molecular models of NS3 protease variants of the Hepatitis C virus |
title_sort |
Molecular models of NS3 protease variants of the Hepatitis C virus |
author |
da Silveira, NJF |
author_facet |
da Silveira, NJF Arcuri, H. A. Bonalumi, C. E. de Souza, F. P. Mello, IMVGC Rahal, Paula [UNESP] Pinho, JRR de Azevedo, W. F. |
author_role |
author |
author2 |
Arcuri, H. A. Bonalumi, C. E. de Souza, F. P. Mello, IMVGC Rahal, Paula [UNESP] Pinho, JRR de Azevedo, W. F. |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Universidade de São Paulo (USP) Instituto Adolfo Lutz (IAL) Instituto Butantan |
dc.contributor.author.fl_str_mv |
da Silveira, NJF Arcuri, H. A. Bonalumi, C. E. de Souza, F. P. Mello, IMVGC Rahal, Paula [UNESP] Pinho, JRR de Azevedo, W. F. |
description |
Background: Hepatitis C virus (HCV) currently infects approximately three percent of the world population. In view of the lack of vaccines against HCV, there is an urgent need for an efficient treatment of the disease by an effective antiviral drug. Rational drug design has not been the primary way for discovering major therapeutics. Nevertheless, there are reports of success in the development of inhibitor using a structure-based approach. One of the possible targets for drug development against HCV is the NS3 protease variants. Based on the three-dimensional structure of these variants we expect to identify new NS3 protease inhibitors. In order to speed up the modeling process all NS3 protease variant models were generated in a Beowulf cluster. The potential of the structural bioinformatics for development of new antiviral drugs is discussed.Results: the atomic coordinates of crystallographic structure 1CU1 and 1DY9 were used as starting model for modeling of the NS3 protease variant structures. The NS3 protease variant structures are composed of six subdomains, which occur in sequence along the polypeptide chain. The protease domain exhibits the dual beta-barrel fold that is common among members of the chymotrypsin serine protease family. The helicase domain contains two structurally related beta-alpha-beta subdomains and a third subdomain of seven helices and three short beta strands. The latter domain is usually referred to as the helicase alpha-helical subdomain. The rmsd value of bond lengths and bond angles, the average G-factor and Verify 3D values are presented for NS3 protease variant structures.Conclusions: This project increases the certainty that homology modeling is an useful tool in structural biology and that it can be very valuable in annotating genome sequence information and contributing to structural and functional genomics from virus. The structural models will be used to guide future efforts in the structure-based drug design of a new generation of NS3 protease variants inhibitors. All models in the database are publicly accessible via our interactive website, providing us with large amount of structural models for use in protein-ligand docking analysis. |
publishDate |
2005 |
dc.date.none.fl_str_mv |
2005-01-21 2014-05-20T14:00:20Z 2014-05-20T14:00:20Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1186/1472-6807-5-1 Bmc Structural Biology. London: Biomed Central Ltd., v. 5, 8 p., 2005. 1471-2237 http://hdl.handle.net/11449/21342 10.1186/1472-6807-5-1 WOS:000234256300001 WOS000234256300001.pdf 7991082362671212 0000-0001-5693-6148 |
url |
http://dx.doi.org/10.1186/1472-6807-5-1 http://hdl.handle.net/11449/21342 |
identifier_str_mv |
Bmc Structural Biology. London: Biomed Central Ltd., v. 5, 8 p., 2005. 1471-2237 10.1186/1472-6807-5-1 WOS:000234256300001 WOS000234256300001.pdf 7991082362671212 0000-0001-5693-6148 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Bmc Structural Biology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
8 application/pdf |
dc.publisher.none.fl_str_mv |
Biomed Central Ltd. |
publisher.none.fl_str_mv |
Biomed Central Ltd. |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808129340155625472 |