Introduction:
Human immunodeficiency virus (HIV) protease enzyme is one of the most promising therapeutic targets for acquired immunodeficiency syndrome (AIDS) treatment. Due to mutation of the virus, there is always a room for new agents.

Material and methods:
The aim of in silico molecular docking study was to analyze and compare the binding mode of seven Food and Drug Administration (FDA)-approved HIV protease enzyme inhibitors, and to understand their structural requirements to inhibit an enzyme by using Schrodinger model as well as to evaluate a free energy of binding of these inhibitors with an enzyme.

Results:
The binding mode analysis showed that the active site was present at the interface of two chains A and B of the enzyme and the crucial amino acid remained responsible for the binding of inhibitors to the HIV-1 protease, which could help to classify the inhibitors as better drug targets. Results of this comparative binding mode analysis of seven FDA-approved drugs could be potential and useful for designing of a new effective inhibitor of HIV-1 protease. Out of seven inhibitors drugs, only two drugs present the best inhibition. HIV protease-nelfinavir complex with PDB: 2Q64 and HIV protease D30N, and R41A double mutant-tipranavir complex in PDB: 1D4S double mutant V82F and I84V, were used as templates for applying the mutations on HIV protease active site. Furthermore, the structure-based computer-assisted search for the comparison of the two inhibitors of HIV protease was completed. On the other hand, tipranavir seems to be a broad specificity inhibitor, as no changes in the bond lengths with the introduction of mutations were observed.

Conclusions:
Tipranavir could be targeted more effectively for designing future drug analogues, as it is less vulnerable to mutations. HIV mutants reported in this study could also be used for preliminary identification of specific inhibitors, as drugs that may alter the HIV protease activity for medicinal use.