Eliram Reyes-Powell, Protein Modelling using Rosetta: Internship | Week 2

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My name is Eliram Reyes-Powell and I am interning at University of California, Davis, School of Medicine in the Department of Physiology and Membrane Biology, with Dr. Vladimir Yarov-Yarovoy and PhD Candidate Brandon Harris. This is the second week of the internship, so make sure you check the first week’s blog!

This week started with the integration of a new member into the Internship, another 2020 Pintern, Carmen Puentes Flores. During this week I have tried to help Carmen as much as I can so that she can get to pace with what we did in the first week. This has helped reinforce my knowledge as well as spot weaknesses in my understanding, so that I could ask Mr. Brandon Harris about it and clarify my doubts. I can’t stress enough how important collaboration is and how thankful I am that Mr. Harris is always willing to help and mentor me in the best way possible.

With respect to Foldit, a Rosetta-based video game, this week I was able to reach level 38/38 which meant that I had finished the intro puzzles and that I could start a soloist competition puzzle. However, a day after I finished “all” the levels, Foldit uploaded a new level, which I still have to work on. So far, Foldit has been very helpful and very fun to play. I started a Beginner puzzle (in soloist mode) about Covid-19. It consists of forming a low-energy state protein that can form many hydrogen bonds with a Covid-19 protein, in order to attach to it. I was able to reach place 97/188 with 12,380 points which is good for the first time (The best score is ~13,600). It is very challenging to think of new ways to obtain a better protein since, sometimes, you have to be willing to lose every single point in order to form a structure that may or may not result in a higher score. We, the interns, share our experiences with Foldit at the beginning and end of every week which is very fun and creates a better collaborative environment.

Beginner puzzle (Covid-19) soloist competition:

As I briefly introduced last week, I was able to utilize the supercomputer cluster, Barbera, to access the Rosetta software. This week, Mr. Harris taught me how to create my “work” directory and sub-directories for each protein I will work with. After I created the needed directories, Mr. Harris showed me how to send my Folder (Which contained the 6uz0 protein I prepared through Chimera and its Electron Microscopy map) to Barbera, from my local directory. It took me a while to understand what the commands were communicating to the computer since they look very complex at first, but Mr. Harris was very patient and answered all of the questions I had. A lot of organization skills are needed to succeed and, although I consider myself very organized, I still struggled at times. In the end, organization is a skill that can always be improved and it is very important to develop it. Being able to access Barbera, feeling comfortable using the commands, memorizing and understanding them, made me feel very accomplished and even more motivated to continue to learn and run the programs on the proteins I was assigned.

Protein 6uz0 with fit Electron Microscopy map.

The application Mr. Harris prepared for this week was the Relax application. It is the second step needed to perform the GALigandDock protocol. The Relax application changes the structure of the protein to have a lower-energy state (so the folding occurs spontaneously or, at least, with minimal aid.) For this step, as I mentioned earlier, organization is critical and, after having some problems running the program, I realized the files weren’t correctly placed. What I take out of this experience is to follow directions as well as possible, to organize myself better, and to ask questions that are necessary and will contribute to my and the other interns’ understanding. The Relax application is a key step for protein modelling, so I am glad we were able to learn about it not only conceptually, but through computational experience as well.

This second week was very challenging and every time I was able to correctly execute a task, I felt very happy and rewarded. The Computer Science aspect of the internship isn’t my strongest area, but I have a good understanding of it and, most importantly, the motivation to continue to learn. The biology and chemistry aspects of the internship come easier to me, but I continue to learn new things every day which is very exciting.

Outside of my internship, I visited my grandparents in Cimarron, CO. I lived in Cimarron last year, so it is very nice to visit when I have the availability. I have been reading a lot and I finished TWO books this week: “Physics of the Future”, by Michio Kaku and “Lazarillo de Tormes”, anonymous. I am also building a list of books, since I will have a lot of free time in August and I want to make the most out of it to both exercise my mind and continue to learn.

 

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