Two of the most important classes I took as a graduate student were CHE542, also known as chemical biology, and CHE 536, also known as molecular modelling of biological molecules. In both classes, we discussed many different aspects of biology. Both were in my second semester as a graduate student. The classes cemented my very positive impression of the academic atmosphere at Stony Brook. Salve Regina gave me a great environment to get my understanding of chemistry started, and Stony Brook quickly felt like the perfect place to truly extend my knowledge.
In CHE 542, emphasis was placed on understanding mechanisms of biochemical transformations. As Professor Peter Tonge famously said, biochemistry is organic chemistry in water. Indeed, water is the solvent of life, and living things have optimized reactivity of organic molecules for their purposes using well placed amino acids. We discussed different types of proteases including serine, cysteine, and aspartate proteases and their importance in biology. We also discussed important stories in the history of drug discovery and chemical biology such as the application of anti-metabolites as anti-biotics. Lastly, we discussed drug-target binding kinetics and its relevance to drug discovery. Overall, a very enriching experience. The final assignment was to write a generic proposal for a grant. I will share this assignment below for public viewing. It involves some interesting experiments that would help characterize the effect quorum sensing inhibitors would have on bacteria. At some point in the future, I would love to carry out some of these experiments.
In CHE 536, the application of computational chemistry programs was explored. Interestingly, part of the class was making a tutorial of how to apply the programs we actually learned how to use. These tutorials include the ones I made for the 2016 class. Professor Rizzo’s resources have been extremely helpful for my learning computational chemistry. The main link to the tutorials is located at https://ringo.ams.stonybrook.edu/index.php/Rizzo_Lab_Information_and_Tutorials.
Ultimately, the class project was based on performing molecular modelling and creating a report on the project. I chose to continue my undergraduate work via virtual screening of quorum sensing proteins. Quorum sensing inhibition is a very attractive mechanism of reducing pathogenicity of bacteria. I took a key quorum sensing protein in Pseudomonas aeruginosa named LasR and docked several thousand molecules into the binding site for assessment. At the time, the PDB ID 2UV0 was the best model at the time for virtual screening of new inhibitors. The co-crystal ligand of 2UV0 is the cognate ligand and natural agonist of LasR, a five membered lactone ring derived from intramolecular cyclization of the amino acid serine. This was not the best structure to virtual screen with since it may have yielded other agonists of LasR thus not yielding the desired phenotype of inhibited quorum sensing. In any case, a few interesting compounds emerged from this modelling and I encourage anyone with a lab to test any of these compounds. I have done further screening of new potential quorum sensing inhibitors which I will discuss in a future post. Until next time, enjoy.
