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What's a good application to thread a sequence over a peptide (of a peptide-protein complex) and minimize?

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What's a good application to thread a sequence over a peptide (of a peptide-protein complex) and minimize?

Hi all,

I have a scenario where I have a peptide-protein complex. I would like to thread a series of sequences over the peptide, then minimize the peptide-protein complex. The idea being, I would like to tell which threaded-peptide-sequences would be the "best" binder predictors. Or at least be able to segregate between potential non-binding sequences and binding sequences.

I've been looking at the backrub protocol. Would this be an appropriate application? I don't see immediately how I can thread the sequences over the peptide with this application then.

Then I've looked at the threading protocol. This looks like I can thread the series of sequences over the peptide, but I'd need fragment files for each new sequence? I don't exactly want this because I know the starting conformation of the peptide (even if I'm attempting to vary the sequence).

Then I've seen the fold and dock protocol. This looks decent because I know the starting conformation of the peptide when docked to the protein, but again, how can I thread a series of sequences over the peptide? And it a full fold-and-dock overkill?

Any advice would be greatly appreciated.

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Tue, 2013-02-12 08:19

It sounds like you want flexpepdock (

Generally if you have the _same_ length on all your peptides, you can do the "threading" trivially with fixbb, and then produce models any way you like: relax, backrub, flexpepdock...

If you have _different_ lengths, especially if you want indels, then the problem rapidly becomes much more complicated...I think the ab initio mode of flexpepdock is a good bet.

Tue, 2013-02-12 08:36

I would have the same length for all the threaded sequences (it's only a 7-mer peptide). So I guess this opens doors as far as which protocol to use for minimization?

I hadn't thought of FixBB (I don't know how I missed that), so I'll use that to thread the sequences. Then maybe backrub to minimize? Or would a full relax be better?

Tue, 2013-02-12 08:55

Sorry for the delay in reply...the forum system is being upgraded and forgot to keep sending me emails when others ask questions.

Backrub, relax, and refinement FlexPepDock are all options. I would use FlexPepDock because it is designed for the purpose, then relax as a second choice because I understand it better than backrub, and then backrub last. (Nothing wrong with backrub!) Frankly, this is a pretty empirical choice: all will work okay for the general purpose; try all three and see which gives the most consistent results!

Tue, 2013-02-19 08:48

Hi All,
How to thread a longer sequence on a smaller peptide? suppose I got peptide of length 7 and I want to thread sequence of length 13.
/\/\/\ to ---/\/\/\---, I mean I want to keep the middle portion threaded over available peptide BB conformation and give terminal residues extended conformation. I will use FlexPepDock in next stage to model the peptide.
I found a way to do this using PyRosetta but looking a alternative easier approach.

Thu, 2013-05-02 16:23

You may want to think about using the Remodel application:

It will be included in the next release of Rosetta, Rosetta 3.5, which should be released fairly soon.

I recently added this to the PyRosetta documentation if you havn't already seen it:

Fri, 2013-05-03 07:44

In my experience PyRosetta is probably about as easy as it gets for doing this. There is no generic "extension" module. I tried to write one and discovered that for everything but simple C-terminal extensions it's all corner cases.

Fri, 2013-05-03 11:55