How to Design a Protein from Primary to Quaternary Structure?

[neuro.akn]

Homework Statement

I am to create "my own" protein that follows the primary structure, then can be formed to follow the secondary structure, and so on until of course the quaternary structure. I am looking for some help on creating my protein so that it meets these needs (first follows the primary structure and can form into the rest of the structures of proteins). Any starting points for my protein will be greatly appreciated. Thank you.

Homework Equations

The Attempt at a Solution

 

[epenguin]

Don't know what the question means. Are you asking about the experimental methods for creating a new, engineered, protein? Are you asking about how to design a protein, e.g. so as to be a catalyst with certain given properties? It is a very broad question and we don't know where you are starting from or why.

 

[Borek]

It sounds as if you were planning to create a protein in which the secondary structure ("can be formed to follow the secondary structure") is forced upon the protein. That's not how it works, secondary structure is in general already defined by the primary structure and can't be changed.

 

[neuro.akn]

I am to create a protein that follows the primary, secondary, tertiary, and quaternary structures (essentially how to design a protein). Borek, I believe you misinterpreted my thread; I do understand that the secondary structure is defined by the primary structure. I am looking for some tips on how to get my primary structure started so that it meets the necessary criteria for defining the secondary structure and then tertiary, and so on and so forth.
Thanks.

 

[epenguin]

I am to create a protein that follows the primary, secondary, tertiary, and quaternary structures (essentially how to design a protein). Borek, I believe you misinterpreted my thread; I do understand that the secondary structure is defined by the primary structure. I am looking for some tips on how to get my primary structure started so that it meets the necessary criteria for defining the secondary structure and then tertiary, and so on and so forth.
Thanks.

Still obscure what the question is. The science that would enable you to design a totally new protein with some function does not exist AFAIK. All the known proteins have their primary, secondary,... structures, so nature has solved a lot of such problems. But to design a new one, well protein engineering consists of producing small modifications of existing proteins. This allows study of the role of e.g. given amino acid residues. Now a principal tool of protein chemistry. Of course there it is OK and useful to produce proteins that don't work in some respect. Which reminds me there is much information to be obtained (not all that easily) from Nature's different designs and variations on a molecule like hemoglobin. So you'd have to take some fairly (but not too) well studied protein like that, find out what has been done with it in this way and see if you could come up with some idea for some other variation with some purpose. But that doesn't sound to me a job of a few hours of an individual or even several together.

 

[Ygggdrasil]

There has been some work in being able to computationally design proteins sequences that will fold into a user-defined structure. I have never used these programs, so I don't know how well they work, but here's one example: Liu and Kuhlman 2006 RosettaDesign server for protein design Nucleic Acids Res: 35, W235. PMCID:1538902 (there may be newer better programs than this, but this is one I remember hearing about).

 

[neuro.akn]

Thank you everyone. The question was obscure, I understand, but it is as simple as that; it is essentially to modify an existing protein so that your "new" primary structure (actually modified from an existing protein) follows the structures of a protein. Thus, it will be able to form the subsequent structures (secondary, tertiary, etc.). That being said, I have now developed a primary structure of which I can go off. Thank you anyways!

 

[epenguin]

It would lighten up our dull lives a bit if you told us what protein you start with and whether there is any particular reason for the choice, and later on what modifications you come up with and any criteria or predictions.

I think hearing solutions found could be, if not a rule here, something of a norm with advantage.

 

[neuro.akn]

Well, I did not start with a particular protein per se. I did look at insulin and a few examples on the internet and in my biochem textbook, however. They were just generic protein structures that I went off of and improvised. I formed a protein structure with two coils in an Alpha-Helix, which then forms into a Beta-Pleated Sheet due to the location of Proline R-groups.

 

[epenguin]

For an up to date view on a protein design strategy (and the fantastic things now possible and being done) there is this article "Computational design of ligand-binding proteins with high affinity and selectivity" Nature 501 p212 12 Sept preceded by a presentation on p177. Only a specialist would understand what all the technical methods are but you could get a rough overall idea.