Homology Modeling Doubts

Question

[Elmo]

Hi,

I am new to Homology Modeling and I really feel that what I did was not really right. Please, I need some advice / comment. I have a protein sequence of 500aa in length and did a BLAST on my protein sequence. Only the 150 - 470aa belongs to a common domain but the residues from 1 - 149 and 471 - 500 doesn't show any common domain. Thus, I break them into fragments (1 - 149, 150 - 470, 471 - 500) and I used HHpred to search for templates and modeled them out individually. Is it right? Now I'm not very sure how can I join them together.

Previously, what I did was inputing the whole protein sequence (1 - 500aa) and letting HHpred to do loop modeling for the regions from 1 - 149 and 471 - 500. Then when I check it with Verify3D and other verification programs, they "complain" for those region being loop-modeled. I am not sure if i can proceed with this model for further investigation like docking and so on. However, the region that was covered (150 - 470) was the part I am targetting for docking later. Can I still proceed? Or align them by fragments like mention earlier? If yes for the later, please can someone please tell how to join them back together.

Thanking you in advance.

Best regards, Elmo

[Khader Shameer]

You can also use HARMONY (Server here:http://caps.ncbs.res.in/harmony/ ; Manuscript here: http://www.ncbi.nlm.nih.gov/pubmed/16844999) to see the compatibility between sequence and structures.

Answer 1

[João Rodrigues]

If you are modelling something for docking, usually you can worry only about the domain that is participating in the interaction. If the flanking domains are not important for the interaction, don't use them.

Now, about the modelling, if you can model domain per domain and all are relevant, that's good. I-TASSER is probably going to do the same thing but refine it a bit better. HHPred does produce usually very fast and not very refined models. You might want to submit them to a refinement procedure afterwards just to get things a bit better stereochemically before the docking.

[Elmo]

Thank you @Joao

Answer 2

[Pappu]

Check out I-Tasser and compare your current models. You can score the models by ProQ.

[Elmo]

Hi @Pappu, thanks for your kind reply. Do you I mean that I superimpose my model to I-tasser's?