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Re: [modeller_usage] How does Modeller handle multiple structures?

Zoe Katsimitsoulia wrote:

1. How will modeller handle the 10 template sequences (which themselves
show a significant amount of variation at certain key positions). More
specifically, a particular area of my seq alignment may read like this:

template 1 xxxxxGxxxxxxxx
template 2 xxxxxTxxxxxxxx
template 3 xxxxxGxxxxxxxx
template 4 xxxxxGxxxxxxxx
template 5 xxxxxGxxxxxxxx
template 6 xxxxxGxxxxxxxx
template 7 xxxxxGxxxxxxxx
target     xxxxxTxxxxxxxx

In simple terms, would modeller in this case use the coord of T in the
template 2 sequence because it matches the target at that location, or
will it use G because it is predominant in the majority of the
structures?
Check the Modeller papers. Modeller doesn't use the coordinates directly, but other properties of the templates, and it uses a weighted sum over all templates. For instance, the Ca-Ca distances of the target would in this case be modeled by a sum of gaussians, where the peak positions correspond to the observed distances in the templates and the weights to the template weights. The templates are weighted by local sequence similarity, which would probably favor the 'T' sequences in this case (but I can't tell for sure because the neighboring residues are considered too, which you haven't shown). You should look at the .rsr file that Modeller produces to see which restraints it's using (although it's not that easy to read). 


2. The 10 template structures I am using are themselves in different
states, for example, partially closed conformation, open, transition,
inhibitor bound, etc. Is this beneficial to building my model or more
detrimental? I am assuming the former based on the logic that the more
info I am giving to modeller, the better my model should be.
However, perhaps there is something about the way modeller works which I
have not grasped that means its actually doing more harm adding the
structures in different states?
The target will be constrained to look as much like a weighted sum of the templates as possible, so you probably want to have the templates in the same state as your desired target state. 

	Ben Webb, Modeller Caretaker
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