Molecular models of NS3 protease variants of the Hepatitis C virus
| Autor: | Walter Filgueira de Azevedo, Isabel M V G C Mello, Paula Rahal, João Renato Rebello Pinho, Nelson José Freitas da Silveira, Fátima Pereira de Souza, Carlos Eduardo Bonalumi, Helen Andrade Arcuri |
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| Přispěvatelé: | Universidade Estadual Paulista (Unesp), Universidade de São Paulo (USP), Instituto Adolfo Lutz (IAL), Instituto Butantan |
| Rok vydání: | 2005 |
| Předmět: |
Models
Molecular Protein Folding Protein Conformation medicine.drug_class medicine.medical_treatment Molecular Sequence Data Drug design Hepacivirus Computational biology Viral Nonstructural Proteins Biology Crystallography X-Ray Ligands Antiviral Agents Protein Structure Secondary Structural bioinformatics Protein structure Structural Biology Databases Genetic medicine Chymotrypsin Amino Acid Sequence Homology modeling Enzyme Inhibitors Databases Protein lcsh:QH301-705.5 Internet NS3 Protease Serine Endopeptidases Computational Biology Genetic Variation Virology Protein Structure Tertiary lcsh:Biology (General) Structural biology Drug Design Multigene Family Antiviral drug Peptides RNA Helicases Research Article |
| Zdroj: | BMC Structural Biology, Vol 5, Iss 1, p 1 (2005) BMC Structural Biology Web of Science Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP |
| ISSN: | 1472-6807 |
| DOI: | 10.1186/1472-6807-5-1 |
| Popis: | Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2014-02-26T17:23:58Z No. of bitstreams: 1 WOS000234256300001.pdf: 1197276 bytes, checksum: cc2ee7126ce555d8e5202993cb882d27 (MD5) Made available in DSpace on 2014-02-26T17:23:58Z (GMT). No. of bitstreams: 1 WOS000234256300001.pdf: 1197276 bytes, checksum: cc2ee7126ce555d8e5202993cb882d27 (MD5) Previous issue date: 2005-01-21 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T14:00:20Z No. of bitstreams: 1 WOS000234256300001.pdf: 1197276 bytes, checksum: cc2ee7126ce555d8e5202993cb882d27 (MD5) Made available in DSpace on 2014-05-20T14:00:20Z (GMT). No. of bitstreams: 1 WOS000234256300001.pdf: 1197276 bytes, checksum: cc2ee7126ce555d8e5202993cb882d27 (MD5) Previous issue date: 2005-01-21 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. UNESP, Dept Phys, IBILCE, Sao Jose do Rio Preto, SP, Brazil USP, Dept Microbiol, Inst Biomed Sci, BR-09500900 São Paulo, Brazil Adolfo Lutz Inst, São Paulo, Brazil UNESP, Dept Biol, IBILCE, Sao Jose do Rio Preto, SP, Brazil Instituto Butantan, Ctr Appl Toxicol, São Paulo, Brazil UNESP, Dept Phys, IBILCE, Sao Jose do Rio Preto, SP, Brazil UNESP, Dept Biol, IBILCE, Sao Jose do Rio Preto, SP, Brazil |
| Databáze: | OpenAIRE |
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