Farheen Zaman

Studying the Binding of Small Molecules to the Exo Site of HIV Protease Using Docking Techniques

Faculty mentor: Dr. Brian Fuglestad

Department: Chemistry

In a nutshell: I have been essentially designing different molecules and testing how well the molecules bind to an [exo site], an auxiliary site in the protein HIV protease, [which] could possibly change the shape of the entire protein. Through testing, I am looking for possible precursors to drugs that would be able to change the shape of HIV protease and therefore render it inactive.

In a bigger shell: HIV protease inhibitors are often used as part of antiretroviral therapy. However, HIV rapidly develops resistance to current HIV protease inhibitors, which target HIV protease’s active site. Binding inhibitors to an allosteric “exo site” of HIV protease may allow for the development of HIV protease inhibitors to which newer strains of HIV are less resistant. Using the Swissdock docking software, the binding affinities of various small molecules to the HIV protease exo site were estimated through simulations. The free energy of binding a small molecule at various conformations to HIV protease was calculated through the Swissdock algorithm, then analyzed to develop small molecules with progressively better binding to the exo site. In the future, these best-performing molecules can be analyzed in lab with various assays to more accurately determine their binding affinity to HIV protease.

End of year goal: Although other anti-HIV drugs have been created that target the active site of HIV protease, many new strains are resistant to these drugs. By designing a drug made of up various fragments that bind to HIV protease's exo site, these resistant strains can be more easily targeted. 

A tip for others: Patience is very important for this type of work. My progress has been somewhat gradual, but nevertheless it is progress and something to be celebrated!