Navegando por Assunto "Protease"

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Acesso aberto (Open Access)
Análise conformacional da enzima protease do HIV-1 relacionada à resistência ao inibidor Nelfinavir
(Universidade Federal do Pará, 2017) HOLANDA, Luiz Henrique Campos; SILVA, Jerônimo Lameira; http://lattes.cnpq.br/7711489635465954; SOUSA, Maisa Silva de; http://lattes.cnpq.br/1775363180781218
The Human Immunodeficiency Virus (HIV), which causes acquired immunodeficiency syndrome (AIDS), is a retrovirus that has highly virulent glycoproteins that invade the CD4 + T lymphocyte through its CCR4 and CXCR5 receptors. The biological cycle of HIV is mediated by the protease, transcriptase and integrase enzymes. HIV-1 protease is an enzyme that is present in the final phase of the biological cycle, where virus maturation occurs, and is an important pharmacological target. The main objective of this project is to verify the effects of the D30N, I84A and M46I mutations on the HIV-1 protease enzyme and the complex formation with the nelfinavir inhibitor through molecular dynamics and bioinformatics techniques. The results based on the structural analyzes showed structural differences between the studied systems. The 1OHR system presented a closed conformation, the systems D30N and D30N_I84A_M46I presented semi-open conformation and the D30N_I84A system presented open conformation, in which the latter presented lower free energy value and greater instability in the RMSD analyzes, however the greater flotation of residues Of amino acids. The theoretical analyzes showed the importance in the resistance of the double mutation D30N_I84A and the conformational restructuring capacity of the M46I mutation and catalytic capacity.
Acesso aberto (Open Access)
Usando a dinâmica molecular para avaliar o impacto que as mutações na protease do HIV-1 produzem na interação da proteína com o antirretroviral darunavir
(Universidade Federal do Pará, 2019-03-29) CUNHA, Karoline Leite; BARROS, Carlos Augusto Lima; http://lattes.cnpq.br/8902921733540173
The emergence of drug-resistant strains used in antiretroviral therapy grows alarmingly on a global scale. Antiretrovirals used in the treatment of first and second line HIV are the ones that most have case reports of resistant strains. Protease inhibitors are a class of antiretroviral drugs that play a key role in AIDS treatment regimens. In addition to the emergence of resistance to IPs used in the usual treatment regimens, Darunavir, a protease inhibitor used in therapeutic rescue treatment, is already reported in patients who already have failed initial treatment and proven resistance. The aim of this work is to evaluate, identify and quantify HIV-1 3UCB protease mutations, as well as to evaluate, through molecular dynamics simulations, the impact that mutations produce on the interaction of 3UCB and its darunavir ligand when compared to the native HIV-1 protease 4LL3 complexed to the same linker.The results obtained in this study showed that the 3UCB multi-resistant HIV-1 protease had a slightly more stable binding profile than the native HIV-1 protease complex 4LL3, with binding free energy results -68.77 and -64.62 kcal / mol, respectively.