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Author Topic: Why is there is no statistical explanation for protein folding?  (Read 248 times)

Offline puppypower

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It has been know for over 50 years that proteins fold with exact folds. Statistical theory predicted an average fold, but not a unique fold. That this exception to statistical theory remains unsolved today, after 50 years of intense research effort, highlights a two-fold failing of statistical methods: firstly, they did not predict the existence of a stable folded state, and secondly, once given as an experimental fact, they still cannot explain it.


 

Offline evan_au

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Quote from: puppypower
It has been know for over 50 years that proteins fold with exact folds...an experimental fact
It has been known for over 30 years that proteins sometimes misfold into different shapes, causing disease.
See: https://en.wikipedia.org/wiki/Prion#Discovery

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Statistical theory predicted an average fold, but not a unique fold
An important class of proteins, the enzymes, do not have a unique fold.
They are amazing, flexible machines, with multiple moving parts which selectively bind to a substrate and then cleave it into the desired products, all in the presence of relevant solvents.
https://en.wikipedia.org/wiki/Enzyme#Induced_fit_model

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they did not predict the existence of a stable folded state
Getting a protein into a crystal form so it can be studied via X-Ray crystallography is a black art. We don't have a general method that will produce a stable folded state - perhaps because the folded shape is so complex and variable, and crystallization loses some of the solvent.

Fortunately, progress with X-Ray lasers has allowed the study of protein microcrystals in the femtosecond before they disintegrate.
See: https://en.wikipedia.org/wiki/X-ray_crystallography#Free_electron_laser

Some human intuition has succeeded in identifying some more stable folding patterns; the Foldit citizen science game has identified some protein structures that defied computer assembly.
See: https://en.wikipedia.org/wiki/Foldit
 

Offline puppypower

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This is not a new theory, but an observation by Chemist, J.G. Watterson. Statistical methods predict an average protein fold, due to the assumptions of thermal energy and vibrations in solution. But as far back as 50 years ago, it was shown that many proteins will fold with exact folds. Exact folds will have a  probability of 1.0. This have little to do with statistics, yet there is no statistical explanation or addendum to address this. My question was a polite way of asking, why is this problem, being hidden in the closet for so long? Why does the statical model get a free ride?

My theory is statistics is a powerful tool that relies on certain assumptions; rules for swinging the hammer. The tool has worked out so well, that many started to assume the assumptions of the tool, reflect the assumptions of reality, and not just the parameters of using the tool. The result is the tail wagging the dog; tool defines reality. The observation of protein folds points out that the assumptions of the tool; tail, is wagging the dog; reality. I thought that science is supposed to evolve when observation requires it.

Maybe a new assumption of the tool can be; reality has situations, like protein folding, that are rational and not defined by statistics. However, to use the tool, we need to ignore these exceptions and assume even they are random. This will make it easier to swing the hammer. Is this already the unwritten assumption?
« Last Edit: 22/09/2016 12:36:07 by puppypower »
 

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