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Offlinewyldeman007
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Can someone tell me
    #8648696 - 07/17/08 08:53 PM (15 years, 9 months ago)

(preferably a molecular biology major) why a protein's tertiary conformation always falls into it's native structure with no alternates given the infinitesimal amount of possible configurations? Is the reason known to science yet?


--------------------

"We are going to die, and that makes us the lucky ones. Most people are never going to die because they are never going to be born. The potential people who could have been here in my place but who will in fact never see the light of day outnumber the sand grains of Arabia. Certainly those unborn ghosts include greater poets than Keats, scientists greater than Newton. We know this because the set of possible people allowed by our DNA so massively exceeds the set of actual people. In the teeth of these stupefying odds it is you and I, in our ordinariness, that are here." - Richard Dawkins

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OfflinePlasmid
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Re: Can someone tell me [Re: wyldeman007]
    #8649109 - 07/17/08 10:36 PM (15 years, 9 months ago)

Quote:

wyldeman007 said:
(preferably a molecular biology major) why a protein's tertiary conformation always falls into it's native structure with no alternates given the infinitesimal amount of possible configurations?




It doesn't.  In a given system composed of some very large number of protein molecules, that protein will occupy a distribution of different conformational positions.  The favored conformations will be the lowest energy states, but proteins do not simply occupy one rigid conformation and stay there.

(and I'm much better than a molecular biology major - I'm a physical organic chemist turned biochemist - I do structural and physical studies on proteins)

I really should say that a population of proteins will have the largest proportion of molecules occupying the tertiary conformation of the native state.  This is considered to be a result of the energy landscape of different conformations.  The native conformation will have the lowest energy associated with it, so as a protein folds, it can be conceptualized as falling down the valleys of the free energy landscape.  Not every protein in a population will fold into the native conformation.  Some proteins will misfold.  Misfolded proteins can undergo aggregation, proteolysis or can be refolded by chaperones.

There are a number of reviews on the topic.  I just happened to glance at a few on my hard drive: listed below.  Search Entrez for "protein folding" and check out the reviews.


Dobson, CM.  The structural basis of protein folding and its links with human disease.  Phil.Trans. R. Soc. Lond. B.  356, pp. 133 - 145.  (2001)

Mogk, A., Mayer, MP., Deuerling, E.  Mechanisms of Protein Folding: Molecular Chaperones and Their Application in Biotechnology.  ChemBioChem.  3, pp. 807 - 814.  (2002)

Edited by Plasmid (07/17/08 11:04 PM)

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Invisiblejohnm214
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Re: Can someone tell me [Re: Plasmid]
    #8649528 - 07/18/08 12:48 AM (15 years, 9 months ago)

Yep, it doesn't.



Yave you ever seen graph's like this?

[image] http://www.lsbu.ac.uk/water/images/drysurf.gif [/image]

All these points on the surface of this dimple thing are possible configuration.  The lower the surface is(like in the center) the lower energy the protein is.


Generally the lowest energy configuration is thought to be the native configuration (edit: conformation), ,however; as you know from things like reacti8on coordinates and such- just cuz something is the lowest energy path doesn't mean things will proceed down that path anytime soon.


My table's lowest energy state is as CO2 and H20- combusted or at least oxidized.  Unless I add fire it takes forever.


So too with many proteins.  Without their chaperones, which help them fold correctly, they'll never get to their native state.w

Edited by johnm214 (07/18/08 09:05 AM)

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Offlinezouden
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Re: Can someone tell me [Re: johnm214]
    #8650144 - 07/18/08 08:23 AM (15 years, 9 months ago)

The rules that govern a protein's tertiary configuration are quite simple, but because there are so damn many possible configurations it becomes very difficult to predict computationally.

In nature, the protein can move through the different configurations much faster than computers can. So they very quickly take their natural state - though as the others have said, many (most?) proteins require additional proteins called chaperonins to help them fold properly. There's also additional factors like temperature and pH.


--------------------
I know... that just the smallest
                                                part of the world belongs to me
You know... I'm not a blind man
                                                    but truth is the hardest thing to see

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Offlinewyldeman007
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Re: Can someone tell me [Re: zouden]
    #8651570 - 07/18/08 03:20 PM (15 years, 9 months ago)

Oh! thanks guys, very interesting stuff and great resources! The only reason I ask is that I was watching a lecture on the subject of proteins when the professor implied a grand mystery to the folding process. She called it "the protein folding problem" and the "Levinthal paradox", that's what I'm very curious about.

If you're at all interested, here's the video: Fast forward to 5:17 - 9:00



Thanks guys you're great!


--------------------

"We are going to die, and that makes us the lucky ones. Most people are never going to die because they are never going to be born. The potential people who could have been here in my place but who will in fact never see the light of day outnumber the sand grains of Arabia. Certainly those unborn ghosts include greater poets than Keats, scientists greater than Newton. We know this because the set of possible people allowed by our DNA so massively exceeds the set of actual people. In the teeth of these stupefying odds it is you and I, in our ordinariness, that are here." - Richard Dawkins

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Invisiblejohnm214
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Re: Can someone tell me [Re: wyldeman007]
    #8653214 - 07/18/08 10:32 PM (15 years, 9 months ago)

OMG, is that your prof?  Can I get a phone number?  What a beutiful flower of chemistry...


(I'm being mean, but somehow all the girls in chem look like that, same weight anyways, at my school at least.)


She's kinda exagerating things though.  I know they can predict the secondary domains pretty well from the primary structure, and from their infer tertiary structure to some extent...

I mean it is a bitch, but its not like you need to consider every fucking possible position.



The other issue is that the most stable conformation isn't necessarily the native conformation... so it's not possible to know the tertiary structure just from knowing the primary structure... I believe they generally use that computer modeling to just understand the folding process wehre you know primary and tertiary structures but don't know the actual folding process.  The whole thing seems dreadfully boring to me, they're always recruiting computer kids and such at my school to help in those projects modeling folding or some P.Chem problem with liggand binding and shit... bleh





LOL, zouden.  I always call those things chaperons instead of chaperonin.... and I did it above in my previous post :/


I always imagine a lunch lady watching the proteins dance and fold :smile:

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Offlinewyldeman007
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Re: Can someone tell me [Re: johnm214]
    #8655803 - 07/19/08 04:33 PM (15 years, 9 months ago)

AH very good, and nope she's just a prof on youtube. I'm sooo looking forward to this kind of stuff...

thanks again..


--------------------

"We are going to die, and that makes us the lucky ones. Most people are never going to die because they are never going to be born. The potential people who could have been here in my place but who will in fact never see the light of day outnumber the sand grains of Arabia. Certainly those unborn ghosts include greater poets than Keats, scientists greater than Newton. We know this because the set of possible people allowed by our DNA so massively exceeds the set of actual people. In the teeth of these stupefying odds it is you and I, in our ordinariness, that are here." - Richard Dawkins

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InvisibleGumby
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Re: Can someone tell me [Re: johnm214]
    #8656337 - 07/19/08 07:16 PM (15 years, 9 months ago)

Ehhh, there are some hot chicks into chemistry. My freshman year chem professor was good looking for her age, just sucked at teaching :lol:


LOL! Random, but I just went to my old college's website to find a pic of the prof, and this was a headline:

http://oxford.emory.edu/news/detail.dot?inode=28767&pageTitle=Concerning%20the%20matter%20of%20the%20zebra:

Concerning the matter of the zebra:
April 23, 2008

As most of you will have heard, a zebra was stolen from a nearby farm and left on the third floor of Seney Hall sometime last night.


Hah, anyway, lets see if I can find her...

http://oxford.emory.edu/dotAsset/28042.jpg

Christ Jesus that image is big, hopefully you're using firefox so you can shrink it to fit. You'd think a bunch of chem professors could figure out how to resize a picture for the website, but they're a bunch of old people who don't like computers :smirk:

The other female chem professor isn't that bad looking either:
Errr... Just saw the pic full size, she's pretty from a far but far from a pretty. Anyway, if you're interested, here's a pic:

http://oxford.emory.edu/dotAsset/27962.jpg

It's a shame the young chem professor isn't there anymore, she was hawt.

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