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I am trying to understand what is protein folding and how it could help cure some diseases.

When reading articles about it, it looks like the goal is to find perfect folds for proteins because some diseases are due to proteins that don't fold correctly. I don't understand why do we need to find them in the first place? Don't correctly folded proteins already exist in the body of people who aren't affected by those diseases? Why do we need to manually find those structures instead of simply "reading" the structure of the correctly folded proteins in the body of non affected people? In the end, is the goal to find the best structure or to find the folding proecess ? Or both ?

Thank you!

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  • $\begingroup$ Please try to make the title of your questions as specific as you can. "Questions about" should never be included. They are all questions, so this is superfluous. Your question is about protein folding, so say what it is you want to know about. I have done this for you. If it is not your question then modify it. $\endgroup$ – David Dec 30 '16 at 21:11
  • $\begingroup$ @David Can't understand what you meant by "If it is not your question then modify it" ? $\endgroup$ – Trevör Dec 30 '16 at 21:12
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    $\begingroup$ I mean, if the title does not reflect what you want to ask, then change it so that it is. I have interpreted it from the content of your question, but it is your question so you should improve the title if you are not happy with it. $\endgroup$ – David Dec 30 '16 at 21:15
  • $\begingroup$ @David Oh ok ! Thank you for the edit ! Yes I should pay more attention to that. $\endgroup$ – Trevör Dec 30 '16 at 21:16
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Protein folding is a complex thing. There are huge computer algorithms and huge mainframes which are trying to predict the final 3D structure of a protein.

Knowing the tertiary and the quaternary structure of a protein, allows us to understand why diseases happen. In many cases a mutation of the gene provokes an aberrant protein folding. When the protein is misfolded, it is not able to do its function. This particular condition is called "Proteopathy".

http://link.springer.com/article/10.1385%2FMN%3A21%3A1-2%3A083

If you know the structure of a protein, you are able to design or improve drugs which can directly influence the protein structure and/or function, for example antibody therapies against cancer (Cetuximab-->against EGFR, in colorectal cancer; it is a drug which was very much improved when computers prediction/simulations are used).

https://en.wikipedia.org/wiki/Cetuximab

It is hard to find out a protein's structure - for some proteins it can require years!

So you first go from the sequence of the healthy people, then you sequence their genomes, and you use this as reference for the people with certain diseases. You might find eventually some mutation is in certain loci in the genomes of people with a certain disease. Then you can study the protein structures, so you can design some new drugs which might tackle this protein. If the protein is misfolded, like the tau protein in the neurodegenerative diseases, then is good to study the structure of this misfolded protein so you can design some drugs for these protein too.

So in the end the structure is extremely important, but often times you have to study many stages of the protein folding process to understand the possible final structure that one protein might have in the body and/or in a certain disease.

I hope this can help!

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  • $\begingroup$ I think you mean neurodegenerative not neurovegetative. $\endgroup$ – David Dec 30 '16 at 21:39
  • $\begingroup$ Cetuximab and nearly all other monoclonal antibodies on the market today were designed the old-fashioned way - by immunizing animals (mice in this case), screening their naturally-produced antibodies, and either humanizing it for direct use (older mAbs, like this one) or having it undergo affinity maturation via several different formats, including applying knowledge of drug/target structures (only the most recent mAbs in development). Unless you can accurately describe this in your answer, I'd just take that whole section out, because it implies the drug was designed, when in fact it was not. $\endgroup$ – MattDMo Dec 31 '16 at 2:01
  • $\begingroup$ Thank you for your comment, please check this link ncbi.nlm.nih.gov/pmc/articles/PMC2803018 $\endgroup$ – flavinsky Dec 31 '16 at 8:33
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An article, Protein Misfolding and Degenerative Diseases, covers this question, and although it focuses on a single type of disease, this is of great importance.

To summarize, there is the potential for misfolding in proteins because of the small differences in energy between different alternative folded states, and because during synthesis some proteins expose to the solvent regions that are hidden in the folded protein and if exposed would make the protein unstable. (These latter require other proteins to help them fold.) Thus, it is not difficult to envisage circumstances in which misfolding occurs, with concommitant loss of function and harmful consequences. The particular current interest in this is because certain neurodegenerative diseases involve misfolding of proteins. Indeed, in Alzheimers and other diseases the amyloid protein folds into an alternative structure to normal.

Although it may be a little advanced, the 10th November 2016 issue of Nature has a series of reviews on this topic, which are free to view. One by Riek and Elsberg deals particularly with the alternative structure.

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