Hi,
I have a structure with a small molecule bound in the active site. There are missing residues in the structure, how can I model it? I tried without the small molecule but it forces the neighbor loop to go in the active site and definitely I don´t want that.
Sudeep
On 12/14/21 6:22 AM, Karki, Sudeep wrote: > I have a structure with a small molecule bound in the active site. There > are missing residues in the structure, how can I model it? I tried > without the small molecule but it forces the neighbor loop to go in the > active site and definitely I don´t want that.
Just add the residues that are missing in your template structure to the target sequence, aligned with gaps in the template. One example is at https://salilab.org/modeller/wiki/Missing%20residues
Ben Webb, Modeller Caretaker
Hello,
I just want to point out that, especially as the missing loop is close to the active site and can reach it directly, presumably it could play a significant role in gatekeeping, activation, stabilization of the bound state, etc. Thus, one probably has to take care in interpreting the resulting model because any specific conformation of the loop will be more or less random and not necessarily relevant to a particular state of a protein. Perhaps the dynamics of the loop (with and without bound ligands) should be further analyzed.
Best regards Eugene
On 15.12.2021 05:06, Modeller Caretaker wrote: > On 12/14/21 6:22 AM, Karki, Sudeep wrote: >> I have a structure with a small molecule bound in the active site. >> There are missing residues in the structure, how can I model it? I >> tried without the small molecule but it forces the neighbor loop to >> go in the active site and definitely I don´t want that. > > Just add the residues that are missing in your template structure to > the target sequence, aligned with gaps in the template. One example is at > https://salilab.org/modeller/wiki/Missing%20residues > > Ben Webb, Modeller Caretaker
Thank you all for the suggestions.The missing residues are near the active site. These missing residues are supposed to be unstructured and in the cryo-EM map I cannot see the density - basically can’t model this region. Of course, the structure we have is with the small molecule bound and for MD work I would like to get the complete structure. Is there any way the modeler can read “HEATOM” - so that I could model the missing residues using the small molecule bound structure as input in modeler. Earlier,I removed the small molecule and tried to build the complete model in Modeller - in this case, the missing residue formed a loop and was placed in the small molecule binding region that is wrongly placed . I agree that the dynamics of the loop with and without bound ligands need to be further analyzed.
Sudeep
________________________________ From: modeller_usage modeller_usage-bounces@salilab.org on behalf of Eugene Radchenko genie@qsar.chem.msu.ru Sent: Wednesday, December 15, 2021 12:46 PM To: modeller_usage@salilab.org modeller_usage@salilab.org Subject: Re: [modeller_usage] Modelling missing residues
Hello,
I just want to point out that, especially as the missing loop is close to the active site and can reach it directly, presumably it could play a significant role in gatekeeping, activation, stabilization of the bound state, etc. Thus, one probably has to take care in interpreting the resulting model because any specific conformation of the loop will be more or less random and not necessarily relevant to a particular state of a protein. Perhaps the dynamics of the loop (with and without bound ligands) should be further analyzed.
Best regards Eugene
On 15.12.2021 05:06, Modeller Caretaker wrote: > On 12/14/21 6:22 AM, Karki, Sudeep wrote: >> I have a structure with a small molecule bound in the active site. >> There are missing residues in the structure, how can I model it? I >> tried without the small molecule but it forces the neighbor loop to >> go in the active site and definitely I don´t want that. > > Just add the residues that are missing in your template structure to > the target sequence, aligned with gaps in the template. One example is at > https://salilab.org/modeller/wiki/Missing%20residues > > Ben Webb, Modeller Caretaker _______________________________________________ modeller_usage mailing list modeller_usage@salilab.org https://salilab.org/mailman/listinfo/modeller_usage
On 12/15/21 4:36 AM, Karki, Sudeep wrote: > Is there any way the modeler can read “HEATOM” - so that I could > model the missing residues using the small molecule bound structure > as input in modeler.
If you mean HETATM then yes, of course; see https://salilab.org/modeller/10.2/manual/node18.html for an example.
Ben Webb, Modeller Caretaker
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Eugene Radchenko -
Karki, Sudeep -
Modeller Caretaker