Hi modellers,
I'm trying to build a homology model of a multi-chain heteromeric protein (with model-default.py script) using as template a homomeric protein as showed in the following example: #begin of "ali" file >P1;pdb structureX:pdb:1:A:10::::: AAAAAAAAAA/ AAAAAAAAAA/ AAAAAAAAAA/ AAAAAAAAAA/ AAAAAAAAAA*
>P1;ABBAB sequence::::::::: AAAAAAAAAA/ BBBBBBBBBB/ BBBBBBBBBB/ AAAAAAAAAA/ BBBBBBBBBB* #End of "ali" file
The model is built normally. However, I noticed that many residues in the active site (which is localized in the interface between each pair of monomers) that are supposed to exposed are turned inside out. I tried to model just as homomeric and so all important side chains in the active site kept the template position. Is there anything I can do to make the modeled residues to adopt the same position as in the template? Would it be reasonable? I'd appreciate any help!
Best regards,
Josmar Rocha
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Josmar R. da Rocha wrote: ... > The model is built normally. However, I noticed that many residues in > the active site (which is localized in the interface between each pair > of monomers) that are supposed to exposed are turned inside out.
This is probably because your starting structure contains steric clashes between the sidechains in the interface region, and the easiest way the optimizer found to minimize these clashes was to bury the sidechains. You could try building multiple models - each model will have a different starting structure and so chances are that at least some of them will not have this problem. Or you could take the .ini file (starting structure) from your first run, and modify it manually (perhaps with something like PyMol's sculpting) to put your interface residues in a sensible position, to guide the optimizer towards the desired solution. Or you could add some restraints to those sidechains to keep them exposed - perhaps upper bound distance restraints between Cbetas in the two chains.
Ben Webb, Modeller Caretaker