All of this is old hat to molecular biologists, but it never ceases to amaze me how intricate God's design for the world is. In a sadder way, it also amazes me that anyone can look at a system like this and not see it pointing toward the Creator. Scientists who have devoted their lives to studying the mechanisms of protein folding, or DNA replication, or any number of amazing systems in creation can look up from their studies and say "Nope, no evidence of intelligent design here." The odds that all of this just happened, and continues to happen is staggering. It's like I'm winning the lottery a billion times every time I breathe.
Sunday, September 25, 2011
Protein crystallography
This is something that amazes me on a regular basis, and I'd like to share it with you. Scientists have figured out the structure of proteins like the one pictured here, as well as thousands of others. Why does that matter? Many new antibiotics and cancer-treatment drugs are "designer drugs", targeted at a specific protein. They are designed to match part of their target protein just like a key in a lock in order to minimize collateral damage to other parts of the body. Understanding protein structures also helps us understand metabolism, the immune system, and many other intricate systems of the body.
Proteins are too small to see in detail even with the most powerful microscopes, so let's back up a step and try a similar problem on a more tangible scale. Say I handed you a crystal (or prism) and asked you to describe it. Not too tricky, right? You might notice that it makes interesting patterns of light across the wall when it catches the sun. If you were comparing it to a different crystal, one of the differences would be how they scattered light in different patterns. Now I'm going to ask you to describe a new crystal, but you can't see the crystal itself. I'm going to put the crystal inside a black box so you can only shoot light in one side, and see the scattered light on the other side. I'll put the crystal on a stick so you can rotate it, and you can take pictures of the scattered light. Can you describe the crystal in the box now without peeking? Scientists called crystallographers have solved this problem for protein crystals to the point where they are describing crystals they've never seen before on a daily basis. Welcome to the world of X-ray protein crystallography.
It turns out that it's a lot of work to coerce proteins into forming regular crystalline structures, and when it does work they make very small crystals, maybe as big as a human hair is thick (100 microns). So handling the crystals is tricky, and positioning them exactly in an X-ray beam the size of a pencil lead requires "telemicroscopes", which are cameras with 4-foot long lenses that magnify things 2 feet away by 1000x. Once everything is lined up, you take pictures using an X-ray detector as you rotate (or "scintillate") the crystal through different axes using very precise motors.
The diffraction images go to a computer, but you don't get a protein structure yet. What you get is something that looks like a negative mold or impression of the structure -- you can tell which parts in 3D space had something in them, and which parts didn't. A simple protein might leave a sort of tunnel-shaped space to be filled. The crystallographer already knows which molecules make up the protein and in what order (thanks to DNA sequencing), but that just makes a long chain until you fold it up. Fitting the chain into the mold is a work of art, as each bond between atoms can rotate in various amounts, and the atoms making up the protein attract and repel each other differently. Once the crystallographer has figured out the best way to fold up the chain to fit in the mold, they publish it for use by other scientists and pharmaceutical companies. The amazing thing is that all the equipment and algorithms are simply reproducing a process that every human body does millions of times a day: folding a new protein into the correct shape.
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