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De novo loop modeling using pyrosetta

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De novo loop modeling using pyrosetta

I want to model loop regions for an already solved structure of my protein. I want to replace the loop regions with new loop segments which are longer in size than the original ones present in the structure + the sequence of the loop should also be different. I want to know whether this can be achieved by using the pyrosetta suite and if so .. how can it be done..


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Sun, 2011-01-16 17:38

This can certainly be done (well, assuming your release of Pyrosetta has the loops namespace wrapped). The question is how complicated is it. If you're asking for a script that will do it, I don't think there is one. I can offer advice on writing the script. Which did you want?

Wed, 2011-01-19 06:57

I really appreciate for ur help and prompt response.. What I was thinking that if I create a decoy set of loops containing 9 , 10 ,11 ... so on fragment loops taken from pdb and use the loop modeling script is that possible ??
or .. otherwise what do u have to say about it and one more thing I want to know that in order to get a grip on programming for pyrosetta script what do I need to do ...

Wed, 2011-01-19 16:56

The best way to handle loops of different length is with different starting structures. Trying to handle multiple length loops in one Rosetta run is challenging; the residue numbering changes as you add residues and things get messed up.

The fastest way to make the starting structures is to create PDBs with the appropriate numbers of residues in the loops (either by deleting residues or copying the coordinates of one residue repeatedly), then run the loop modeling code with the build_initial option. (I don't know how to access that by pyrosetta but it's in the regular loop modeling executeable's documentation someplace.)

Once you have those, it sounds like you want pretty much standard loop modeling with occasional design steps. You can pick apart the existing loop modeling protocols (or perhaps call them directly from pyrosetta), then separately integrate design steps. Design is easy, just run the PackRotamersMover with a PackerTask/TaskFactory that allows for design at the loop positions.

If you don't already know python, it may be easier to just do this as repeated applications of the Rosetta loop modeling and fixbb executeables. You can iterate like so:
loop modeling (to create starting structures of different lengths)
fixbb (sequence diversity)
loop modeling (loop diversity)
fixbb (sequence diversity)

It's not nearly as fast as just coding design directly into the loop modeling steps would be, but it's faster than spending several months learning to code in python and/or C++.

Thu, 2011-01-20 07:15

Latest version have test/ and test/ scripts that could be seen as demo/examples for loop modeling so please check them out.

Mon, 2011-01-24 10:23