I am using I-TASSER to model a protein of more than 2000 amino acids for MD simulation but the highest limit of the sequence in I-TASSER is 1500 amino acids. How do I solve this problem? One way is to model 1500 amino acid separately and then the rest of the sequence but in that case how do I join together two models? Is there an alternative way to that?
Hi Rishi!
Guessing that your protein might have multiple domains, and provided that you already know if certain domains interact with each other or not, there is a way to model such proteins, albeit with slightly questionable precision. What you can do is the following:
1. Find out the boundaries of each of your domains in the sequences and trim them: model them individually if they are known to exist individually. It will be helpful if you have prior information about the stability of these protein domains in solution in the absence of other domains, as well as any hint of certain domains interacting with each other through ITC, SPR or even native PAGE.
2. For domains which you think might interact with each other, you may try using a (G)n linker in the sequence before submitting it for homology modelling. I myself have not tried it, but I don't see any reason that it shouldn't work.
3. If this works, or the 1500+500 way of inputting sequences for modelling work, you may try the completionist program to model loops between them. The models of these loops are not meant to be used to infer their structural characteristics, but just as convenience to use them for MD and related studies. The link can be found here:
http://opig.stats.ox.ac.uk/webapps/medeller/home.pl?app=Completionist
Hope this helps!
Hi,
Agree with Arunab, model your structure in part. Also, Try to use chimera modeller (homology modeling) for structure prediction.
Thank you both of you for the answer. I have already modeled the protein in parts. Assembled them together and have submitted to the completionist for the modelling of the loops.
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