Studying HIV infection closely, there are particular proteins associated with HIV’s particular type of infection called latency. Latency refers to HIV’s dormant stage of infection where its genetic information is present in the host cell’s genome, but not yet triggered or activated to create more viruses. Histone deacetylase 1 has been found to be associated with HIV latency through previously conducted studies. Histone deacetylases plays a role in controlling gene expression by regulate the acetylated state of the histone proteins and modifying the accessibility of genes to transcription enzymes. Targeting HDAC1 may mean limiting the expression of HIV genes already integrated into the host genetic information. Targeting the viral gene reservoir would remove the major barrier against curing HIV.
What drug candidate would be the most effective at targeting Histone Deacetylase 1 (HDAC1)? To determine this, Ajahn Tom’s lab uses a combination of chemistry, biochemistry, cell culture and computational techniques. Using an autodocking program, I predict and screen potential drug candidates that target HDAC1. This process is an inexpensive way to determine compatibility between potential drug candidates with protein of interest. As we all know, wet lab is very expensive and this computational method reduces the cost of trials until absolutely necessary. Following the computational work, the data is analyzed via PLS and SOM mathematical models and low binding energies between the drug and protein. The final pool of around drug candidates is then applied to biochemical assays and then cell culture.
Though my work is in the primary stages, every day of work in the lab leads to progress towards the goal of determining effective drug candidates that target HDAC1.
Till the next update,