biostudies-literatureMachado LACoordenação de Aperfeiçoamento de Pessoal de Nível Superior170https://www.ebi.ac.uk/biostudies/studies/S-EPMC7468422biostudies-literatureUnknown7HIV-1 integrase is the enzyme responsible for integrating the viral DNA into the host genome and is one of the main targets for antiretroviral therapy; however, there are documented cases of resistance against all the currently used integrase strand transfer inhibitors (INSTIs). While some resistance-related mutations occur near the inhibitor's binding site, the mutation N155H occurs on the opposite side of the drug-interacting Mg²⁺ ions, thus, not interacting directly with the drug molecules and currently lacking an explanation for its resistance mechanism. Moreover, mutation N155H and the resistance-related mutation Q148H are mutually exclusive for unknown reasons. In the present study, we use molecular dynamics simulations to understand the impact of the N155H mutation in theFrontiers in molecular biosciencesEvidence for Disruption of Mg²⁺ Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors.PMC7468422(CAPES) - Finance Code 001Machado LAGuimaraes ACRfalseEvidence for Disruption of Mg²⁺ Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors.HIV-1 integrase is the enzyme responsible for integrating the viral DNA into the host genome and is one of the main targets for antiretroviral therapy; however, there are documented cases of resistance against all the currently used integrase strand transfer inhibitors (INSTIs). While some resistance-related mutations occur near the inhibitor's binding site, the mutation N155H occurs on the opposite side of the drug-interacting Mg²⁺ ions, thus, not interacting directly with the drug molecules and currently lacking an explanation for its resistance mechanism. Moreover, mutation N155H and the resistance-related mutation Q148H are mutually exclusive for unknown reasons. In the present study, we use molecular dynamics simulations to understand the impact of the N155H mutation in the2020-01-01T00:00:00Z20202026-04-14T03:10:10.566Z2025-05-31T23:51:51.128ZS-EPMC74684223297438310.3389/fmolb.2020.00170