BCH377, our advance laboratory course for specialist students in Biochemistry, Immunology and Molecular Genetics, is an applied biochemistry techniques course. Our hearty and resilient group of students joining from; out of the city, province and country this semester. How could we maintain the objective of teaching practical biochemistry during the COVID fall semester of 2020?
Well the answer was to take equal parts outstanding, and I mean outstanding, specialist students, and brilliant, intelligent and creative TAs and mix for one month. The result, Wilson Zheng, a graduate student from Regis Pomes lab, developed a stunning experimental module that our students could do from home. He arranged access to the University of Toronto teach clusters for students to run all-atom simulations to calculate the folding properties of WW domain from Pin1. The results are gorgeous. Students used GROMACS to run these simulations, and when you successfully run a command such as gmx_mpi pdb2gmx –f 1pin_ww.pdb which processes their pdb file which they generated from a Uniprotkb sequence. GROMACS will run this command on the teach cluster and roll out your output with a satisfying quote when successful. We had some fun compiling GROMACS says quotes on our discussion board, my personal favourite:
GROMACS reminds you “Whatever happened to Pong?” ~F. Black
We began our semester with half of our students participating from home, and half in person. And, if you have not yet heard, Dr. Ahlia Khan has done beyond an excellent job in ensuring an environment where our students could learn safely. A Herculean task, and for the first four weeks the in-person students were lucky to be able enjoy the fruits of her labours. Our technicians, Quyen and Aida, prepared individual reagent kits, and even equipment set up was individualized. We worked 2-m away with Laura DiGiovanni, their awesome wet lab TA from Peter Kim’s lab. Laura’s group formed what we called our “wet” lab stream and those joining us from home worked on companion computational experiments in the “dry” lab with steersman, Wilson. Students worked in teams of wet and dry lab streams and combined their data in their reports. Things were going along fairly well, and then the University closed to dual delivery Thanksgiving weekend. Wilson’s group had already begun to dive into the showpiece molecular dynamics module and were making excellent progress under his tutelage. Thankfully Andrea Guljas, also from Regis Pomes lab, was able to come in and rescue our wet lab students. Freeing Laura up to develop an awesome image processing and AI analysis module, which is still underway, but the preliminary data is beautiful.
Students, now working hard with both Wilson and Andrea, began to test different force fields to look for optimal condition to monitor the folding properties of the WW domain from Pin1. When Wilson first described what he wanted to do with this module, he directed me to some active research on fast folding WW domain mutants. I watched the simulation movies in awe. But even I, with my novice eyes, could note that these domains all ended in alpha helices. Wilson, are these not meant to be beta sheets? Yes, he replied, that is a common problem. Oh well, alpha helices folding before your very eyes is pretty darn cool – on with the show. But then the students compared this commonly used folding force field with one developed by a former graduate student of the Department of Biochemistry, Dr. Sarah Rauscher. What to our wondering eyes did appear? Three perfect beta-strands organized in crystallographic perfection. Charmm36m, homegrown awesomeness.
In this work, executed by our Specialist students, shown in the movies below, you can observe some amazing things. Watch Diana Lam’s movie showing what happens to the WW domain when you apply force to the two ends of the peptide. Marvel at the perfection of Tony Yu’s refolding of the WW domain using the Charmm36m force field and compare it to the ones Yusef Al-Molieh’s perfectly calculated using the standard Charmm27.
There was some actual sweat represented in this work, there was troubleshooting, there were runs and re-runs of simulations, and ultimately success. And in the end, is that not exactly what learning practical approaches to biochemistry is all about? Look out science, here comes the Faculty of Medicine Specialist BIG class of 2022, a force to be reckoned with.