On 13/03/2024 10:31, VERONICA MARTIN HERNANDEZ via AMBER wrote:
> Hi
> This is not strictly related to AMBER.
> I was trying to make a conformational change in the structure of a protein, but the pdb structure isn't complete, the first 40 residues are missing. What is the best software to complete the missing residues?
> I don't think they affect much the conformational change because they are far from the loop I'm studying, but I'm curious how to solve this problem.
> Thanks in advance
> Vero
Dear Veronica,
assuming that you do need the structure of the first 40 residues, there are different approaches you may take.
In such cases, a good first step is often to try and use some form of homology modelling, also known as comparative modelling. The suite of software I would recommend for this is Modeller
(
https://salilab.org/modeller/). The idea here is that there may be other proteins whose structure is solved that have a very similar sequence, in which case one can infer the structure from these
templates. Modeller is fairly straightforward to use, even though it allows one to tweak a large number of parameters to cover most needs. The online tutorials and manual will go through most of the
commonly encountered situations.
Then, there are cases where good templates are missing. Here, one can use slightly more advanced homology methods. For example, one can use the tools in the PsiPred suite
(
http://bioinf.cs.ucl.ac.uk/psipred/) coupled with Modeller itself. The way this works is by finding proteins whose structure is solved for which there is evidence that they will have a similar
structure to the one expected for your unknown one, regardless of sequence similarity. If you have to go this way and don't want to follow each step yourself, this approach has also been automated,
originally by DMPFold, which is also part of the PsiPred suite, and (much) later on by Alphafold. Both pieces of software do the whole process of template-finding and modelling automatically, and in
addition also consider the statistics of contacts between residues to improve the final predicted structure.
Finally, there are situations where also these more advanced methods fail (I had one such case recently). When this happens, it is almost always because of sheer lack of solved templates. If you end
up in such a situation, you can always fold your protein from scratch, in which case AMBER does an excellent job and also allows you to use a good number of enhanced conformational sampling methods.
I hope this helps. If you don't mind saying what protein you are working on, this could give us a better idea at what you are facing.
Cheers,
Charo
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Received on Wed Mar 13 2024 - 02:00:02 PDT
