Effects of the Q80K Polymorphism on the Physicochemical Properties of Hepatitis C Virus Subtype 1a NS3 Protease
Hepatitis C virus genotype 1a (HCV-1a) comprises clades I and II. The Q80K polymorphism is found predominantly in clade I but rarely in clade II. Here, we investigated whether natural polymorphisms in HCV-1a clade II entailed structural protein changes when occurrence of the Q80K variant was simulat...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-07-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/11/8/691 |
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| author | Allan Peres-da-Silva Deborah Antunes André Luiz Quintanilha Torres Ernesto Raul Caffarena Elisabeth Lampe |
| author_facet | Allan Peres-da-Silva Deborah Antunes André Luiz Quintanilha Torres Ernesto Raul Caffarena Elisabeth Lampe |
| author_sort | Allan Peres-da-Silva |
| collection | DOAJ |
| description | Hepatitis C virus genotype 1a (HCV-1a) comprises clades I and II. The Q80K polymorphism is found predominantly in clade I but rarely in clade II. Here, we investigated whether natural polymorphisms in HCV-1a clade II entailed structural protein changes when occurrence of the Q80K variant was simulated. Based on HCV-1a clade I and II protein sequences, the structure of the HCV-1a Q80K mutant NS3-4A was obtained by comparative modeling. Its physicochemical properties were studied by molecular dynamics simulations and network analysis. Results demonstrate that, in the presence of the K80 variant, clade II protease polymorphisms A91 and S/G174 led to variations in hydrogen bond occupancies. Structural analyses revealed differences in (i) flexibility of the H57 catalytic residue on the NS3 protease and (ii) correlations between amino acids on the NS3 protease and the NS4A cofactor. The latter indicated possible destabilization of interactions, resulting in increased separation of these proteins. The present findings describe how the relationships between different HCV-1a NS3 protease amino acid residues could affect the appearance of viral variants and the existence of distinct genetic barriers to HCV-1a isolates. |
| first_indexed | 2024-12-21T20:34:10Z |
| format | Article |
| id | doaj.art-b41002846f5342a28eedd1084719de7e |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-21T20:34:10Z |
| publishDate | 2019-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-b41002846f5342a28eedd1084719de7e2022-12-21T18:51:09ZengMDPI AGViruses1999-49152019-07-0111869110.3390/v11080691v11080691Effects of the Q80K Polymorphism on the Physicochemical Properties of Hepatitis C Virus Subtype 1a NS3 ProteaseAllan Peres-da-Silva0Deborah Antunes1André Luiz Quintanilha Torres2Ernesto Raul Caffarena3Elisabeth Lampe4Laboratório de Hepatites Virais, Instituto Oswaldo Cruz/FIOCRUZ, Rio de Janeiro, RJ 21040-900, BrazilPrograma de Computação Científica, Instituto Oswaldo Cruz/FIOCRUZ, Rio de Janeiro, RJ 21040-900, BrazilLaboratório de Biologia Computacional e Sistemas, Instituto Oswaldo Cruz/FIOCRUZ, Rio de Janeiro, RJ 21040-900, BrazilPrograma de Computação Científica, Instituto Oswaldo Cruz/FIOCRUZ, Rio de Janeiro, RJ 21040-900, BrazilLaboratório de Hepatites Virais, Instituto Oswaldo Cruz/FIOCRUZ, Rio de Janeiro, RJ 21040-900, BrazilHepatitis C virus genotype 1a (HCV-1a) comprises clades I and II. The Q80K polymorphism is found predominantly in clade I but rarely in clade II. Here, we investigated whether natural polymorphisms in HCV-1a clade II entailed structural protein changes when occurrence of the Q80K variant was simulated. Based on HCV-1a clade I and II protein sequences, the structure of the HCV-1a Q80K mutant NS3-4A was obtained by comparative modeling. Its physicochemical properties were studied by molecular dynamics simulations and network analysis. Results demonstrate that, in the presence of the K80 variant, clade II protease polymorphisms A91 and S/G174 led to variations in hydrogen bond occupancies. Structural analyses revealed differences in (i) flexibility of the H57 catalytic residue on the NS3 protease and (ii) correlations between amino acids on the NS3 protease and the NS4A cofactor. The latter indicated possible destabilization of interactions, resulting in increased separation of these proteins. The present findings describe how the relationships between different HCV-1a NS3 protease amino acid residues could affect the appearance of viral variants and the existence of distinct genetic barriers to HCV-1a isolates.https://www.mdpi.com/1999-4915/11/8/691hepatitis C virusQ80K variantpolymorphismsNS3 proteasesimulationmolecular dynamicsnetwork analysis |
| spellingShingle | Allan Peres-da-Silva Deborah Antunes André Luiz Quintanilha Torres Ernesto Raul Caffarena Elisabeth Lampe Effects of the Q80K Polymorphism on the Physicochemical Properties of Hepatitis C Virus Subtype 1a NS3 Protease Viruses hepatitis C virus Q80K variant polymorphisms NS3 protease simulation molecular dynamics network analysis |
| title | Effects of the Q80K Polymorphism on the Physicochemical Properties of Hepatitis C Virus Subtype 1a NS3 Protease |
| title_full | Effects of the Q80K Polymorphism on the Physicochemical Properties of Hepatitis C Virus Subtype 1a NS3 Protease |
| title_fullStr | Effects of the Q80K Polymorphism on the Physicochemical Properties of Hepatitis C Virus Subtype 1a NS3 Protease |
| title_full_unstemmed | Effects of the Q80K Polymorphism on the Physicochemical Properties of Hepatitis C Virus Subtype 1a NS3 Protease |
| title_short | Effects of the Q80K Polymorphism on the Physicochemical Properties of Hepatitis C Virus Subtype 1a NS3 Protease |
| title_sort | effects of the q80k polymorphism on the physicochemical properties of hepatitis c virus subtype 1a ns3 protease |
| topic | hepatitis C virus Q80K variant polymorphisms NS3 protease simulation molecular dynamics network analysis |
| url | https://www.mdpi.com/1999-4915/11/8/691 |
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