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Author Topic:   re: those impossibly improbable protein folds...
derwood
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Posts: 1457
Joined: 12-27-2001


Message 1 of 5 (28901)
01-12-2003 10:13 AM


Interesting article by M. Denton (yes, that one), discussed here:

http://members3.boardhost.com/john666/msg/40587.html


Replies to this message:
 Message 3 by Tranquility Base, posted 01-12-2003 5:11 PM derwood has responded

    
derwood
Member
Posts: 1457
Joined: 12-27-2001


Message 2 of 5 (28903)
01-12-2003 10:23 AM


The abstract, emphasis mine:

Before the Darwinian revolution many biologists considered organic forms to be determined by natural law like atoms or crystals and therefore necessary, intrinsic and immutable features of the world order, which will occur throughout the cosmos wherever there is life. The search for the natural determinants of organic form-the celebrated "Laws of Form"-was seen as one of the major tasks of biology. After Darwin, this Platonic conception of form was abandoned and natural selection, not natural law, was increasingly seen to be the main, if not the exclusive, determinant of organic form. [i]However, in the case of one class of very important organic forms-the basic protein folds-advances in protein chemistry since the early 1970s have revealed that they represent a finite set of natural forms, determined by a number of generative constructional rules, like those which govern the formation of atoms or crystals, in which functional adaptations are clearly secondary modifications of primary "givens of physics."
[b]The folds are evidently determined by natural law, not natural selection, and are "lawful forms" in the Platonic and pre-Darwinian sense of the word, which are bound to occur everywhere in the universe where the same 20 amino acids are used for their construction.[/i][/b] We argue that this is a major discovery which has many important implications regarding the origin of proteins, the origin of life and the fundamental nature of organic form. We speculate that it is unlikely that the folds will prove to be the only case in nature where a set of complex organic forms is determined by natural law, and suggest that natural law may have played a far greater role in the origin and evolution of life than is currently assumed.


    
Tranquility Base
Inactive Member


Message 3 of 5 (28925)
01-12-2003 5:11 PM
Reply to: Message 1 by derwood
01-12-2003 10:13 AM


We already know that protein folds are dictated by stability and folding rate. The abstract does not reveal what new work Denton et al have done.

The abstract does not really impinge on the debate. A cell still has to randomly stumble upon a sequence that folds and is functional. The post you link to erroneously suggests that the limited useable protein folds makes the odds shorter as if there is some non-random element directing mutations away from the dead ends! There is no such element. Random variation will not be influenced by the number of viable protein folds.

And Happy New Year SLPx.

[This message has been edited by Tranquility Base, 01-12-2003]


This message is a reply to:
 Message 1 by derwood, posted 01-12-2003 10:13 AM derwood has responded

Replies to this message:
 Message 4 by derwood, posted 01-13-2003 12:30 PM Tranquility Base has responded

  
derwood
Member
Posts: 1457
Joined: 12-27-2001


Message 4 of 5 (28993)
01-13-2003 12:30 PM
Reply to: Message 3 by Tranquility Base
01-12-2003 5:11 PM


quote:
Originally posted by Tranquility Base:
We already know that protein folds are dictated by stability and folding rate. The abstract does not reveal what new work Denton et al have done.

Abstracts usually do not contain that, but it does contain their conclusions, which seemed ot me to be important.
quote:

The abstract does not really impinge on the debate. A cell still has to randomly stumble upon a sequence that folds and is functional. The post you link to erroneously suggests that the limited useable protein folds makes the odds shorter as if there is some non-random element directing mutations away from the dead ends! There is no such element.



Funny - I always thought that selection (of various types) is not quite random.
quote:

Random variation will not be influenced by the number of viable protein folds.


Why not? If only X-number of folds are possible, then it seems to me that there are, in fact, not some nearly infinate number of possibilities, which are the basis of the typical "impossibility" calculations/assertions.

quote:

And Happy New Year SLPx.


You too.


This message is a reply to:
 Message 3 by Tranquility Base, posted 01-12-2003 5:11 PM Tranquility Base has responded

Replies to this message:
 Message 5 by Tranquility Base, posted 01-13-2003 5:54 PM derwood has not yet responded

    
Tranquility Base
Inactive Member


Message 5 of 5 (29013)
01-13-2003 5:54 PM
Reply to: Message 4 by derwood
01-13-2003 12:30 PM


SLPx

That issue is on our current journals board. I flipped through the article and will copy it when I locate my copy card.

The article is really a review article with a hypothesis stating what us protein folding people already knew. It's a useful article, don't get me wrong, but it is an opportunistic article basically stating the obvious. I'll let you know if I change my mind after carefully reading it. I have always thought of protein folds as goverened by 'natrual law', my research concerns the computer simualtion of protein folding after all.

Abstracts usually do not contain that, but it does contain their conclusions, which seemed ot me to be important.

I don't agree. Abstracts usually reveal the basic results as well as conclusions. This artilce is primarily a reivew article of some of my favourite protein theoriticians (Chothia, Thornton etc).

Funny - I always thought that selection (of various types) is not quite random.

I'm talking about pre-selection. Selection is non-random but it does not help the cell preferentially mutate to canonical folds.

TB: Random variation will not be influenced by the number of viable protein folds.

SLPx: Why not? If only X-number of folds are possible, then it seems to me that there are, in fact, not some nearly infinate number of possibilities, which are the basis of the typical "impossibility" calculations/assertions.

Again I'm talking pre-selection. What the paper is really about is that if you do an artificial evolution experiemtn (phage display or cell-based) you are likely to end up with a canonical protein fold. It says not much more than that. It will not speed up the result becasue that protein fold still has to have a compatible sequence. It's not like throwing electrons and protons together and getting hydrogen. You need the right sequence. If the sequence is right you get a canoncial fold, sure. That's my honest professional opinion transcending the E vs C debate.

[This message has been edited by Tranquility Base, 01-13-2003]


This message is a reply to:
 Message 4 by derwood, posted 01-13-2003 12:30 PM derwood has not yet responded

  
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