Biology? Physics? Chemistry? Despite of its intimidating name, the course biophysical chemistry is one of the most inspiring one I have ever had, and is regarded as the most popular course by two branches of our students. Eager to know what it is?
All you need is Boltzmann
The core concept of the whole course is the Boltzmann distribution, which tells us how likely a state is according to its energy.
The simplest form of Boltzmann Equation
Hmm….how can we link this awkward mathematical expression to biology? Think of this example: inside a protein, atoms are connected with bonds. Some of these bonds are very strong; the others are weaker. Besides bonds, they can also interact with the surrounding molecules, such as water or its ligand/receptor. Imagine that we know the magnitude of all these bonds and interactions, and the temperature is also given. The question is, can we predict what will happen next? Will the protein unfold spontaneously? If yes, how long will the process take? If no, will the protein binds to other molecules, and how long can this binding sustain?
The answer is, yes AND no. Boltzmann distribution says, it is all PROBABILITY that matters.
Expanding the same concept from a single protein to the entire world of biochemistry, biophysical chemistry digs into the universal physical laws under the complex reactions and ever-changing states, acting as a key to unmask them, and make prediction about the future. It is not difficult to imagine how understanding of biophysical chemistry is essential to pharmaceutical applications, such as study of protein-protein docking and ligand screening in early drug development.
Structure of the course
The course was divided into two parts: three hours lecture in the morning and four hours of computer lab, which is a extension of the content in lecture. In order to pass the course, you need to get a “Pass” grade in all the 8 computer lab assignments (Only Pass/Fail for these assignments). The course is graded as A (highest) to F (fail), which is 100% dependent of the four-hour final exam.
After spending the first lecture reviewing the properties of common biological molecules and interactions, we were introduced the Boltzmann distribution at the first lecture. In the computer lab on the same day, we quickly had a feeling of the effect of sampling on this distribution by trying the simulation by ourselves on computer:
Taking more “steps”, closer the results of simulation to prediction
The same as bioinformatics computer labs, we need to write our own python code. Luckily, we have two experienced teaching assistants, Dari and Björn, who are always around to help us. For some complicated exercise, we were given the scripts as a platform, so that we can make our own beautiful plot based on them:
Examples of random walk, plotted using our Python scripts
Other topics of this course including secondary structure formation, folding and unfolding of protein…… and the most puzzling question of biochemistry: Levinthal’s Paradox. At the end of the course, we were finally led to the application part of biophysical chemistry and were capable of solving a ligand-docking problem on our own:
Can you see the small molecule binding to the large membrane protein?
The amazing course teacher
I cannot end this post without talking about our beloved teacher, Professor Erik Lindahl, who is the soul of this course. Erik (yes, he insists us to call him “Erik” instead professor both in classroom and in Email), is a full professor of biophysics at Stockholm University and KTH Royal Institute of Technology, and also one of the three directors of our master program.
Once you are in touch with Erik, you will be definitely “infected” by his deep fascination in ion channel. He has a large research team in Science For Life Laboratory, working on both “wet-lab” (e.g. protein functional test) and “dry-lab” (e.g. molecular dynamics stimulation). During the course, we were invited to go inside his lab and get an opportunity to see how a real biophysics lab look like:
Wet-lab: study of ion channel in oocyte
Dry-lab: working on simulation software
Student Research Opportunities in Biophysical Chemistry
One of Erik’s major achievements is the development of the software GROMACS, which is a powerful, world-leading molecular simulation tool. Last year, there are two students from our program who did their master thesis in Erik’s Lab. I am so happy to talk to one of them, Oliver Snow. Oliver works on bacterial pH-gated ion channel, which belongs to one of the model systems of ion channels that present in brain. The below “shivering protein” video is part of his degree project, showing the state transition of this protein in microseconds. Of course, the video is made with GROMACS 😉
State Transition in microseconds, video credited to Oliver Snow
This summer, we also have three students who work as summer research fellows in Erik’s lab. Want to know what are they doing? I will talk to them very soon, hopefully in next blog XD. But if you are not patient enough, click here https://www.scilifelab.se/researchers/erik-lindahl/ now to get a brief view about Erik’s study at Science For Life Laboratory!
Last but not least, besides the solid knowledge in biophysics, there is one important thing I learned from this course: in science, there exist no true boundary between subjects (Erik is indeed a physicists by education). As long as you are willing to learn, willing to think and willing to do, there are plenty of research space in science!