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Re: [modeller_usage] Do a loop refinment in order to mimic loop in a template



On 4/28/21 9:30 AM, Miguel Lacerda wrote:
We are modelling 80 isoforms of an enzyme superfamily. In the 1st step we generated the models based on the templates that have higher sequence identity. Now, we are trying to place a loop in a specific conformation. This loop is very important for the enzyme catalysis.  The catalytic site is build up by a Calcium center coordinated with 6 residues. 4 of those are located in the loop that does not have the desired conformation. Our problem is due to the fact that the most of the templates (selected based on their higher identity to the target) did not have calcium in the X-ray structure which displaces the loop. What we are trying now is to refine this problemic region in order to match the only X-ray structure that was solved in presence of Calcium and obtain the ideal conformation for the active enzyme. Do you have any suggestions on how we could achieve this using modeller?

Modeller's loop refinement protocol is probably not going to help you much here, since it will try to model the loop residues in an ab initio fashion - it will not use any information from the templates, and it does not consider specific interactions with ligands or ions. What you probably want to do is build a regular comparative model using two templates - one for the non-loop region (the majority of the sequence) and another that just covers the loop region - and here you'd want to use the structure that has the correct loop conformation. You'll probably need to tweak this a little to make it work nicely, e.g. by ensuring the two templates overlap a bit. See also https://salilab.org/modeller/FAQ.html#1

	Ben Webb, Modeller Caretaker
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