Why is protein folding so important?

I work in a lab that works, in part, on understanding protein folding and misfolding. I'm not involved in this project, but I still find it fascinating and enjoy talking about it. Being around people who are working on it, is obviously interesting too. Anyway, not everyone in my life, outside of the field understands the complexity of the problem, as the language of scientific discussion can pose a barrier, so I thought I'd break it down as best as I can...

Proteins are essential to life and carry out a multitude of tasks in the body; carry the oxygen you breathe, break down the food you eat, attack antigens that could harm your body etc. Each protein is made up of a specific sequence of amino acids and could range from 10 to 500 amino acids long. Now imagine this: Let's say a protein is 100 amino acids long. Since there are 20 kinds of amino acids, there are 20 choices for every single position on that sequence. Which means that there are 20 choices for the first position, 20 for the next and so on, till all the 100 positions have some amino acid on them. Each amino acid has unique chemical characteristics, ranging from how much it likes water, how many electrons it has, whether it is polar (has a negative and positive charge on it) or not, which give the eventual protein its function. The number of combination's of amino acids to make up a sequence of 100 is a massive number. So much so that my calculator can't figure it out. However, it's fascinating in its own right, how nature and evolution have found 1 specific ideal combination of amino acids for whatever purpose that protein is about.

Anyway, this sequence of specific amino acids now has to fold a specific structure in order to function. In vivo and in vitro, proteins fold on the microsecond timescale or lower. That's crazy. So in a tiny, tiny amount of time, no matter how many times one tries it, this seemingly random sequence of amino acids, fold into a specific structure every single time! Think about it. If you had a thread that was 100 units long, with each unit made up of up to 20 colors, would you be able to fold this thread into a shape within a few microseconds into the same shape every single time?

The picture I have shown above is a cartoon of HIV Protease, a 99 residue long dimer (it is made up of 2 chains), and is an example of a folded protein.

So folding is tough, but why is it important?

Well for one thing, proteins are extremely important for our biological function and it would be great to know exactly how they work. And the protein folding issue was initially considered a theoretical problem but now it has medical implications. When proteins don't fold correctly, or misfold, diseases occur. Alzheimer’s disease, cystic fibrosis, Mad Cow disease and some cancers are caused by misfolded proteins. So in order to therapeutically tackle these diseases, it is important to understand why they occur. As a result, understanding the process of folding, and misfolding, will undoubtedly aid us in our quest to cure these diseases.