I have modelled three domains of a protein separately, now I need to join them together for the final protein. I was thinking of loop modelling of the linker protein. Can anyone suggest me some tools for doing the same?
Is there any other approach of doing the above?
Thank you.
Hi,
To be able to have an accurate structure, I suppose there is a complete structural homologue available ? In general, tools for loop remodelling also use structural alignments with close homologues. If you have the three models (and preferably you have a complete structural homologue), use any of the homology modelling tools available that allow you to upload template structures (where you then provide your 3 structural domains, with or without alignment). An example of such a web-server is i-Tasser.
Hope it works !
If you don't have a homologous structure in the PDB bearing all three domains, search for all pairwise arrangement of the three domains (this means searching for different domain architectures). For example, If your domains are A, B, and C, search the PDB (using Blast or HMMER) for homologous sequences bearing AB, BA, AC, CA, BC, or CB domain architectures. With luck, you will find at least two different proteins where your three domains interact with one of your other domains. These template structures will show you the most likely interfaces where your domains interact with each other. From there you can directly model a single polypeptide chain of your domains using comparative modeling (e.g. with MODELLER) or perform docking experiments using the interdomain interfaces you found as constraint (and then model using Modeller). If you find just one template structure in the PDB where only two of your domains interact, model those first and then look for any hydrophobic surface that remain exposed to the solvent. Then perform docking of your remaining domain using the hydrophobic surface as constraint. For example, say you found a template structure in the PDB where domains C and A interact. Use comparative modeling to create a model of your A and C domains interacting. Search for hydrophobic surfaces in the CA model and write down the surface residues. Then perform a docking experiment using your CA and B models, and provide the hydrophobic residues of the CA models as target for docking the B model.
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