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harmonic_Calphas in RosettaLigand flags.txt

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harmonic_Calphas in RosettaLigand flags.txt

For RosettaLigand with some backbone flexibility, I have experimented with adjusting the harmonic_Calphas value from 0.3 to 0.5, 1, and 2.5. I have noticed that there is more backbone motion when I do this. However, is this advisible to adjust? I understand that this value imposes harmonic restraints on the backbone during the minimization step. Why impose these restraints at all? I know the default is 0.3, but how much can this value be safely changed?

I am also curious how many residues around the ligand are allowed to relax in this manner. The paper (2008) says that only a few residues move - but how exactly is this value determined? I am curious because I am running a series of RosettaLigand docking runs on different conformations of a protein (generated by homology modeling from multiple templates) and I would like to know what value to set the harmonic_Calphas value in the flags file to in order that the protein explore most of the conformations existing between the different conformations I've generated.

Thank you,
Charles Kuntz
Ph.D. candidate
Eric Barker's laboratory
Purdue University

Wed, 2010-07-14 08:57

Hello, fellow grad student!

I assume you're talking about the Davis & Baker paper.

As a general rule, with the constraints - you just have to sample to figure out what works. It's likely to be a system-specific result; the more the system is flexible, or the xtal structure is poor, or there's binding site motion, the weaker constraints you'll want.

Your question is deep enough that you may just want to start poking around in the code to figure it out. It would be better if we had perfect documentation, but we don't...

I've contacted the author to see if he has further insight.

Thu, 2010-07-15 06:55

Straight from the author:

I don't really have much more to contribute. "Safe" is a relative term; I agree you just have to try different values and see if you believe the results. The "default" value was based off the benchmarks in my paper, to see what gave the best results.

I don't remember how the mobile residues are determined exactly. I think it's all residues within X Angstroms of the ligand, plus ~2 residues up- and down-stream of those in sequence order. Someone would have to dig in the code to see what X is.

A note from me: "X" appears to be residues having a backbone atom within 7 angstroms, if you look at the code. I could be wrong.

Thu, 2010-07-15 10:47