With all the computational modeling of proteins that we have been learning about, I became really interested in the potential applications it has on drug design. How do computational scientists go about designing drugs? How do they evaluate its efficiency as a drug? What chemical properties must one consider for the drug to be both effective and safe? I began some research and I stumbled upon a short article that briefly described the process in designing HIV protease inhibitors.Back in the 1980’s, HIV was a newly discovered and proved to be an immediate threat to the human population. Scientists quickly discovered the structure of the HIV protease using x-ray crystallography methods and found it was a symmetrical molecule with an active site near its center. Then the fun stuff began.
Scientists took the computerized molecule and critically analyzed every atom. This allowed them to compare possible inhibitor structures to a database and narrow down possible drug structures. In the end an inhibitor was determined by identifying substrates and essentially “gluing” them together to create a symmetrical inhibitor to match the active site. With a few tweaks to the molecular structure the drug Norvir (ritonavir) was created.
To me this entire process was mind blowing! I say this especially because we have learned so much about crystallography and protein structures that it seems like we’re so close to becoming these biochemists that create the next revolutionary drug treatments. I look forward to learning more about computational methods and how these skills can be applied to biological systems!