Integrase and reverse transcriptase are enzymes of the HIV-1 virus and also main targets for studying the inhibition of virus replication in the host cell. With the help of computer simulations, we can predict potential active ingredients. In my master 's thesis, I focused on the study of the binding of integrase and reverse transcriptase inhibitors using computer simulations of molecular docking and molecular dynamics. In molecular docking simulation, I obtained information of the binding sites of the ligand with the protein and the binding energies of various antiretroviral compounds, where bictegravir had the highest binding affinity. I also examined the effect of magnesium ions and DNA strand on the binding strength of the inhibitor at the binding site. The computer - generated dissociation constant values were compared with the experimentally determined values of the concentration of half the maximum effect of the EC50 inhibitor. I also compared the binding energies of different modifications of bictegravir, where the original structure retained the highest value. For the case of bictegravir (original complex, magnesium ion-free complex and magnesium ion-free complex and without DNA), I monitored the change in contacts and type of interactions during the 50 ns long simulation and the change in ligand position in the binding site, conformational changes of the complex and protein upon binding ligand. The same parameters were also analyzed in the case of delavirdine and rilpivirine, which are non-nucleoside reverse transcriptase inhibitors. I compared the results of both computer methods with data from other studies and obtained comparable results regarding ligand contacts with amino acid protein residues and the predominant type of interactions between them.
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