Hello everyone,
I am very new to modelling and working a target sequence that has just less than 27% sequence identity with another 10 proteins that have crystal structures. My target and templates are all myosin proteins, but from 2 different classes, since there are no crystal structures available for my target in its same class.
I have 2 concerns/queries:
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?
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?
Thanks very much in advance,
-Zoe