Modelling Protein Structures

Question

[vijay]

Dear All,

I have a set of 5 gene sequences of the same enzyme , out of which 1 is control and the rest are mutagen exposed groups. I have the conceptually translated amino acid sequence for this set of gene sequence as well. Now, I am trying to a model the structures of these amino acid sequences for both the control and mutagen exposed groups, in order to understand the changes at the structural level.

I just have a question at this point. I feel I should pick the same set of templates for all the sequence and carry out my modelling. However, I just want to confirm if I am on the right track. If not , kindly advice me on how to go about this.

Responses are highly appreciated.

Answer 1

[João Rodrigues]

If you pick the same template for everyone, everyone will look the same, assuming the mutagen causes point mutations here and there and not long deletions. I would start indeed by modelling them using the same template (the original even, if available) and then run molecular dynamics to probe for structural indicators of change (actually probing changes might take some time and accuracy is limited).

[vijay]

Is it worthwhile doing a molecular dynamics on a homology modelled structure? If you could provide me with some paper reference, it would be great.

[João Rodrigues]

If the model is sufficiently good, sure it is. Paper references.. well, maybe this: http://www.molbiolcell.org/content/19/11/4707.long

[vijay]

Thanks for your assistance!! let me try this!!

Answer 2

[afonsomduarte]

I'd start with the same model for all (if the differences between the 5 sequences is not so much i.e point mutations and not stretches of peptidic chains), form this you would get similar models indeed, but then you have to refine these models by energy minimization and molecular dynamics calculations. This last steps will (hopefully) show you the changes between your mutants. PS this strategy works fine when the point mutations are located in key functional sections of the enzymes for example.