What Biologists do all Day - Structural Biology

Do you ever wonder what biologists actually do all day long? Do they sit (stand?) there and brew evil potions with yeast and E. coli while breeding the next killer virus? Torture mice? Lovingly talk to flowers?

First of all, there are many kinds of biologists and many jobs they can have, so it's impossible to make a general statement. But after sitting in front of a computer the whole day, I thought I'd show you one aspect of what the life of a biologist can look like.

And it's the life of a structural biologist.

Don't get me wrong, it's not my profession, just something I have to study for my degree. And it's not something I particularly enjoy, but here we go!

When you're told about the structure of a protein, they'll usually show you something like this:

By Matt Howard

But how do we create such a structure? Because we can't just look through a microscope and see it. And it's not something a computer can just do by itself. It's the end result of a long and tedious process.

First, you need a protein. But not just a single molecule, a lot of it! Correctly folded and as free of contaminants as possible. That alone is already a piece of work. And then, you need to create a protein crystal.

For that, you need the exact right conditions (salt concentration, correct detergent, correct temperature, some luck). Because even if a crystal forms, it might not be one you can use.

This one might look cool, but it's completely useless.

Hemoglobin crystal I made about 2 years ago

This would be a crystal that could be used:

Public Domain

Then, the crystal is put on a tiny metal stick and shot with x-rays, which creates a so-called diffraction pattern that looks like this:

By Jeff Dahl

How this happens exactly and how we proceed from this is complicated and it would go too far to explain it in a short post meant to give you some basic insights. Let's just say it involves a lot of dark magic math and physics (I'm sure you'll find plenty to read about it if you google a bit, in case you're really interested. I'm also willing to answer some basic questions in the comments).

But in the end, you get a picture that gives you the "electron density" at certain points in the molecule. From there, you can create the actual structure, bit by bit. It's work, it can go terribly wrong and it's not something I'd enjoy doing for the rest of my life. I'm impressed by the patience of everyone who chooses to go in this field and stays.

An example of an "electron cloud" with the correct amino acids (the building blocks of proteins) would look like this:

Created by me, today

Let's have a closer look at that!

Also mine

Looks neat, doesn't it? But this is a best-case scenario. Not only do you need to add these lines yourself and basically guess which amino acid it might be (there are several that look the same if presented by the electron clouds)

Mine. And something doesn't look right here!

No, the resolution of the electron clouds can also turn out very, very bad, if the conditions were wrong, your crystal was bad, the x-ray machine sucked or something else just messed up your experiment.

Mine. And how is anyone supposed to work with this?

And why all that? Why would anyone go through all that trouble just to find out the structur of some dumb protein?

The structure of a protein can tell us a lot of how that protein functions (or why it might not function sometimes). This allows us to create similarly working proteins, create models of how cellular processes work, and much more. We need the structures, and we need the people who research them.

But geez, am I glad I don't have to do this all the time.

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Sources: The lectures on structural biology I attend

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