Can different models of the same protein have similar or same Lowest energy levels.

Message boards : Rosetta@home Science : Can different models of the same protein have similar or same Lowest energy levels.

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Jose

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Message 17054 - Posted: 25 May 2006, 12:46:50 UTC

If so, how do you choose which one is the correct one?


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Message 17056 - Posted: 25 May 2006, 14:09:05 UTC

i would assume that, assuming rosetta gets it right, then this could only happen if the protein exists in two such states in nature, which i would expect would be selected against by natural selection, as it is unlikely that the protein will perform the same function equally well in two different states.

I believe there is a different path in the folding process in afflictions such as sickle-cell anaemia, a genetic disease, due to the minor difference in the amino acid sequence between 'normal' haemoglobin and sickle-cell haemoglobin. Although the amino acid sequences are very similar, as the substitution alters the folding of the protien, the resulting structure's may have different low energy levels.
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David Baker
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Message 17060 - Posted: 25 May 2006, 15:38:01 UTC - in response to Message 17056.  

i would assume that, assuming rosetta gets it right, then this could only happen if the protein exists in two such states in nature, which i would expect would be selected against by natural selection, as it is unlikely that the protein will perform the same function equally well in two different states.

I believe there is a different path in the folding process in afflictions such as sickle-cell anaemia, a genetic disease, due to the minor difference in the amino acid sequence between 'normal' haemoglobin and sickle-cell haemoglobin. Although the amino acid sequences are very similar, as the substitution alters the folding of the protien, the resulting structure's may have different low energy levels.



Yes. most proteins have only one very low energy valley. there are some with two, but in these cases both are biologically important so we would be interested in both. (these are proteins which convert back and forth between two states dependent on the conditions, like molecular switches). so far we haven't attempted to model these proteins as the landscapes are more complicated, but it is something we are starting to work on.
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Message boards : Rosetta@home Science : Can different models of the same protein have similar or same Lowest energy levels.



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