Understanding the co-evolutionary molecular mechanisms of resistance in the HIV-1 Gag and protease

Abstract

Homology modelling. Homology modelling of the viral PR and Gag was conducted in MODELLER v.9.16 (Webb and Sali, 2014). To construct the tertiary structures a suitable template was first selected. Accordingly, the atomic coordinates for an HIV-1 subtype C PR bound to NFV (PDB ID: 2R5Q) was retrieved from the PDB (Coman et al., 2008). The 2R5Q PR was resolved by X-ray diffraction to 2.3 Å and did not contain any PI drug resistance mutations. Prior to modelling, the ligand (NFV) was removed and the template and target sequences (viral PR) were aligned in MAFFT (Katoh and Stadley, 2013). The template selected

The HIV-1 Gag Protein Displays Extensive Functional and Structural Roles in Virus Replication and Infectivity

“…In particular, studies on individual Gag domains such as matrix, capsid and nucleocapsid in both mature and immature virions have been evaluated [ 7 ]. While it has been postulated that amino acid variation is observed in HIV-1 non-B vs. B subtypes [ 8 ], sequence analysis and structural studies indicate that strategic amino acid substitutions in Gag may also contribute to drug resistance [ 9 , 10 , 11 ].…”