[Lii]

I currently have a DNA sequence that codes for a known protein. I need to cause a mutation in one of the residues that will cause the resulting protein to be inactive but still fold into the proper 3D structure.

All I know about the protein is its sequence. Its function seems to be unknown.

I can think of ways to render the protein inactive, perhaps with nonsense mutations. I can also think of ways to cause the protein to maintain its 3D structure, like with a synonymous substitution. However, I'm not sure what mutation could leave the protein inactive while also maintaining is 3D structure.

I think I might need to swap one particular amino acid out for another but I'm not sure how to make this decision if I don't know the function of the protein.

[Yggdrasil]

Does the protein have homology to any proteins of known function or any conserved domains?

[Babcock_Hall]

Yggdrasil makes an important point.  All I can think to add at this time is that if there is no assay for function, it is difficult to see how you would be able to test whether or not your mutation had the desired effect.

[Arkcon]

Like everyone has said, yo will have to determine, somehow, what residues code for the active site, and what residues code for the rest of the protein.  Like everyone else, I have no idea how to do that if you have no idea what the function of the protein is.  I do have a question about your application: if you don't know the protein's function, why do you need to have it fold properly, and still remain inactive?  For that matter, how will you know if its inactive or not?

[Lii]

Yes, I think I was just dealt a bad hand with this protein. A conserved domain search brings up one possibility... though the domain had an E value above 4 so it's not too likely.

The question was a matter of let's study the function of this protein by making it inactive which didn't make much sense to me as we don't know the function.