Hello all. Is it possible to do a loop refinment of a model by giving the residue range plus the template (which will hold the desired spatial location)? The orientation of the loop in my model its different to my template’s. I’m trying to refine a model in hope to switch the position/orientation of the loop, but im having dificulties… Regards.
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On 4/22/21 7:24 AM, Miguel Lacerda wrote: > Is it possible to do a loop refinment of a model by giving the residue > range plus the template (which will hold the desired spatial location)?
If you already know the "desired spatial location" then what are you trying to refine?
> The orientation of the loop in my model its different to my template’s.
Modeller does not use the template orientation for loops (many loops correspond to insertions anyway). The starting conformation for a loop is random and is influenced only by the termini positions. See the loop modeling paper or https://salilab.org/modeller/10.1/manual/node499.html
If you want to manually set the starting conformation for the loop, override the build_ini_loop() method: https://salilab.org/modeller/10.1/manual/node96.html
Ben Webb, Modeller Caretaker
Dear Ben, Thank you very much for your email.
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?
Best, Miguel
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De: Modeller Caretakermailto:modeller-care@salilab.org Enviado: 22 de abril de 2021 18:21 Para: Miguel Lacerdamailto:Migueltavlacerda@outlook.pt; modeller_usage@salilab.orgmailto:modeller_usage@salilab.org Assunto: Re: [modeller_usage] Do a loop refinment in order to mimic loop in a template
On 4/22/21 7:24 AM, Miguel Lacerda wrote: > Is it possible to do a loop refinment of a model by giving the residue > range plus the template (which will hold the desired spatial location)?
If you already know the "desired spatial location" then what are you trying to refine?
> The orientation of the loop in my model its different to my template’s.
Modeller does not use the template orientation for loops (many loops correspond to insertions anyway). The starting conformation for a loop is random and is influenced only by the termini positions. See the loop modeling paper or https://salilab.org/modeller/10.1/manual/node499.html
If you want to manually set the starting conformation for the loop, override the build_ini_loop() method: https://salilab.org/modeller/10.1/manual/node96.html
Ben Webb, Modeller Caretaker -- modeller-care@salilab.org https://salilab.org/modeller/ Modeller mail list: https://salilab.org/mailman/listinfo/modeller_usage
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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Miguel Lacerda -
Modeller Caretaker