Hi everyone and welcome to my 2021 Pintern Blog! My name is Anna Bartschi and I’m from the small town of Ridgway, Colorado. I just finished my first week working as an intern for the UC Davis Department of Medicine. Sadly, due to pandemic related restrictions, I am not able to travel to the college campus and have been working with my mentor, Vladimir Yarov-Yarovoy, through Zoom calls. Despite the internship being online, I have already learned so much and am extremely grateful to be able to participate in such interesting research. We have been focusing on how to use Rosetta Commons, an application that runs a variety of programs for drug discovery through coding with Python. Before the internship even began, we were given the tasks of compiling Rosetta and completing the beginner levels of the game Fold-It. As someone who had no experience coding with Python, figuring how to install and compile Rosetta was a challenge, but with a little help from Brandon Harris, my mentor’s student teacher, I was able to figure it out. Playing the game Fold-It was a huge aid in understanding what the internship was about. In each level you are given a different model of a protein and tasked with folding it into the most efficient pattern for its function.
Once the internship started, we downloaded a 3D model of an 5EK0 protein. Using Chimera, another computer application, we edited the protein so that the information was simple enough to be put through Rosetta. The protein has a voltage gated sodium channel. When the receptors on the protein are triggered it opens up the channel sending signals of pain to the brain. Our goal is to attach a ligand to the receptors to stop the channel from opening, therefore minimizing pain in a patient. Once we had the protein ready for Rosetta, we ran it through the Relax program. This refined the structure so it only had the information we needed. After we repeated a similar process and simplified the ligand. We then had to combine the files of our simplified protein and ligand. Finally, we were able to run the GALigandDock program. This program had a complex Python script and will take all weekend to run. It repeatadly calculates different interactions between the protein and ligand until it finds the position with the best efficiency for pain reduction. Attached below is an image of the 3D model of our ligand and protein. The ligand is the small structure with different colors on it.
Besides learning about Rosetta, my mentors have already taught me more important life skills. We went over different ways to read research papers so that you can understand them without spending hours interpreting them. Thanks to everyone who read my post! See you next week!
Very interesting stuff Anna. Appreciate you sharing the details of your internship!