This is the TLDR from the article of the answer to the question "What is protein folding?":
If a protein is essentially a self-assembling nanomachine, then the main purpose of the amino acid sequence is to produce the unique shape, charge distribution, etc. that determines the protein’s function.
The article goes on to talk about other things, like "What if, instead of measuring a protein’s structure, we could predict it?" and that's cool, but it's sort of outside of the scope of the question posed in the title.
I only kind of skimmed that section because it's about this project that is trying to figure out how to predict what shapes proteins fold into. Nifty tech, but not something I care a whole lot about.
(Edit: If that tech interests you, there's also this on HN today: https://news.ycombinator.com/item?id=25253488 and I imagine that's why this was even posted -- because some people are probably wondering "What's a 101 explanation of protein folding?")
Not covered by the article:
Misfolded proteins are the crux of the problem with most genetic disorders. Your body produces this string of protein sequences and it fails to fold up into the unique shape that makes it a useful tool that does a specific job.
(I always think of some old cartoon where two kids are playing with "gender neutral spiffy spiffy high minded description" toy from Switzerland -- think LEGOS only blocks you string together and bend as you see fit -- and their two mothers are talking and then one of the kids folds the bendable blocks into the shape of a gun and says "Bang" and one of the moms is all "Never mind.")
Chemical derangement of the cell can interfere with protein folding. You have these little factories inside the cell that produce protein strings and as they come out, if the climate is chemically deranged (usually pH balance or salt imbalance are the culprits), then it won't fold. It just lays there, a stringy useless mess of protein.
When you cook an egg, the egg white turns white and solidifies due to proteins being denatured. Denatured means they got unfolded.
Sometimes when a protein is denatured -- unfolded -- it's reversible. Sometimes -- like with egg whites -- it's not.
So in some cases if you could figure out why the protein is failing to fold properly, the body can potentially re-use denatured proteins and turn them back into working nanomachines.
And sometimes it can't and then it has to go to some kind of garbage chute in the cell and some serious genetic disorders involve a failed garbage chute, so misfolds can't be effectively removed from the cell, which is a really huge problem. The "garbage chute" is some thing that basically digests the proteins.
You raise very good points about the role of protein folding and quality control in disease. But folding by itself is essentially a physicochemical process. A protein will fold (or its mutant will misfold) within a cell just like it would do it in a test tube.
Don't underestimate the role of structure prediction in human disease. There are proteins known to be involved in disorders where a structure has been impossible to determine by experimental methods (membrane proteins are a known example). And there are still plenty of barely characterized proteins where a structural model might shed light on their function.
> Your body produces this string of protein sequences
A small nitpick: you meant "string of amino acids". In other words, a protein sequence.
> Sometimes -- like with egg whites -- it's not.
Under the right conditions even proteins in coagulated egg white can be renatured.
TIL: Under the right conditions even proteins in coagulated egg white can be renatured.
A small nitpick: you meant "string of amino acids". In other words, a protein sequence
Thank you. You are correct.
Don't underestimate the role of structure prediction in human disease.
I'm not. I just don't really find the tech behind it fascinating. When they start coming out with articles saying "This project has successfully predicted X and this is clinically useful in this way," I'm sure I will read it on the edge of my seat like a gripping thriller.
>When they start coming out with articles saying "This project has successfully predicted X and this is clinically useful in this way," I'm sure I will read it on the edge of my seat like a gripping thriller.
My point is that's a long way off. Like all data driven science, this will be great for forming hypotheses. However, without a falsification hypothesis, and empirical data, it is unlikely to ever reach the point where it's useful clinically.
Okay. I don't see why anyone would feel the need to say that. It seems to miss the fact that my point is that I am not dismissing the importance of this to disease. I'm merely not fascinated by the tech. I said that explicitly, so I would never guess that anyone would think I would need it explained that "This is a long way off."
Edit; The comment I replied to was edited after I began my reply, before I hit "submit." Comment I replied to initially only said My point is that's a long way off.
If a protein is essentially a self-assembling nanomachine, then the main purpose of the amino acid sequence is to produce the unique shape, charge distribution, etc. that determines the protein’s function.
The article goes on to talk about other things, like "What if, instead of measuring a protein’s structure, we could predict it?" and that's cool, but it's sort of outside of the scope of the question posed in the title.
I only kind of skimmed that section because it's about this project that is trying to figure out how to predict what shapes proteins fold into. Nifty tech, but not something I care a whole lot about.
(Edit: If that tech interests you, there's also this on HN today: https://news.ycombinator.com/item?id=25253488 and I imagine that's why this was even posted -- because some people are probably wondering "What's a 101 explanation of protein folding?")
Not covered by the article:
Misfolded proteins are the crux of the problem with most genetic disorders. Your body produces this string of protein sequences and it fails to fold up into the unique shape that makes it a useful tool that does a specific job.
(I always think of some old cartoon where two kids are playing with "gender neutral spiffy spiffy high minded description" toy from Switzerland -- think LEGOS only blocks you string together and bend as you see fit -- and their two mothers are talking and then one of the kids folds the bendable blocks into the shape of a gun and says "Bang" and one of the moms is all "Never mind.")
Chemical derangement of the cell can interfere with protein folding. You have these little factories inside the cell that produce protein strings and as they come out, if the climate is chemically deranged (usually pH balance or salt imbalance are the culprits), then it won't fold. It just lays there, a stringy useless mess of protein.
When you cook an egg, the egg white turns white and solidifies due to proteins being denatured. Denatured means they got unfolded.
Sometimes when a protein is denatured -- unfolded -- it's reversible. Sometimes -- like with egg whites -- it's not.
So in some cases if you could figure out why the protein is failing to fold properly, the body can potentially re-use denatured proteins and turn them back into working nanomachines.
And sometimes it can't and then it has to go to some kind of garbage chute in the cell and some serious genetic disorders involve a failed garbage chute, so misfolds can't be effectively removed from the cell, which is a really huge problem. The "garbage chute" is some thing that basically digests the proteins.