Morphing two GPCR conformations
Dear Chimera-X users! I try to use the morph command to model the conformational change of GPCR related to its activation. Having two superimposed conformations of the receptor, which are different in the position of the internal part of the transmembrane helix VI, I try to visualize the displacement of this helix using morph #2,1 frames 250 Unfortunately the produced trajectory looks very unnatural (one helix overlaps with another one). Would it be possible to improve the accuracy of such morphing e.g. providing some restraints? Many thanks in advance ! Enrico
Hello, All the options are given in the "morph" page ... there is no option for restraints, sorry: <https://rbvi.ucsf.edu/chimerax/docs/user/commands/morph.html> You could try changing any of the parameters that are controlled by the command options described in that page. In my experience, the most useful to try changing is "coreFraction" ... although it is still possible that different options might help for your specific structures. If changing the command parameter values does not seem to help, the most effective method (but also the most work) is to somehow build more intermediate structures that guide the path. In other words, if your structures are A and B, instead of trying to go in one morph from A->B, manually build one or more intermediate structures A', A'', etc. to guide where you want the morph to go and then do multiple stages of morphing A->A'->A''->B. It is not simple, and may take a lot of your time to build these intermediate structures. I hope this helps, Elaine ----- Elaine C. Meng, Ph.D. UCSF Chimera(X) team Resource for Biocomputing, Visualization, and Informatics Department of Pharmaceutical Chemistry University of California, San Francisco
On Aug 22, 2024, at 8:07 AM, Enrico Martinez via ChimeraX-users <chimerax-users@cgl.ucsf.edu> wrote:
Dear Chimera-X users!
I try to use the morph command to model the conformational change of GPCR related to its activation.
Having two superimposed conformations of the receptor, which are different in the position of the internal part of the transmembrane helix VI, I try to visualize the displacement of this helix using morph #2,1 frames 250
Unfortunately the produced trajectory looks very unnatural (one helix overlaps with another one).
Would it be possible to improve the accuracy of such morphing e.g. providing some restraints?
Many thanks in advance !
Enrico
Thank you very much Elaine ! Actually I've already tried to increase coreFraction 5-15 or even 50 and it did produce more smooth movement of the helix. BTW, would it be possible to generate several conformers between two extremums using Chimera-x ? Yours with thanks Enrico Il giorno gio 22 ago 2024 alle ore 18:01 Elaine Meng <meng@cgl.ucsf.edu> ha scritto:
Hello, All the options are given in the "morph" page ... there is no option for restraints, sorry: <https://rbvi.ucsf.edu/chimerax/docs/user/commands/morph.html>
You could try changing any of the parameters that are controlled by the command options described in that page. In my experience, the most useful to try changing is "coreFraction" ... although it is still possible that different options might help for your specific structures.
If changing the command parameter values does not seem to help, the most effective method (but also the most work) is to somehow build more intermediate structures that guide the path. In other words, if your structures are A and B, instead of trying to go in one morph from A->B, manually build one or more intermediate structures A', A'', etc. to guide where you want the morph to go and then do multiple stages of morphing A->A'->A''->B. It is not simple, and may take a lot of your time to build these intermediate structures.
I hope this helps, Elaine ----- Elaine C. Meng, Ph.D. UCSF Chimera(X) team Resource for Biocomputing, Visualization, and Informatics Department of Pharmaceutical Chemistry University of California, San Francisco
On Aug 22, 2024, at 8:07 AM, Enrico Martinez via ChimeraX-users < chimerax-users@cgl.ucsf.edu> wrote:
Dear Chimera-X users!
I try to use the morph command to model the conformational change of GPCR related to its activation.
Having two superimposed conformations of the receptor, which are different in the position of the internal part of the transmembrane helix VI, I try to visualize the displacement of this helix using morph #2,1 frames 250
Unfortunately the produced trajectory looks very unnatural (one helix overlaps with another one).
Would it be possible to improve the accuracy of such morphing e.g. providing some restraints?
Many thanks in advance !
Enrico
Maybe I don't understand your question, but that is exactly what morphing does: it generates intermediate conformers. However, what I said in my previous reply was that if you want the conformers to be different than the ones you got from morphing, you may have to generate them manually in some kind of multi-step process. This could involve manually rotating bonds, or breaking bonds and moving parts around separately before re-forming bonds. Yes you could do all these steps inside of ChimeraX, but there is no simple way to make ChimeraX do the work for you. Elaine
On Aug 22, 2024, at 9:21 AM, Enrico Martinez <jmsstarlight@gmail.com> wrote:
Thank you very much Elaine !
Actually I've already tried to increase coreFraction 5-15 or even 50 and it did produce more smooth movement of the helix. BTW, would it be possible to generate several conformers between two extremums using Chimera-x ?
Yours with thanks
Enrico
Il giorno gio 22 ago 2024 alle ore 18:01 Elaine Meng <meng@cgl.ucsf.edu> ha scritto: Hello, All the options are given in the "morph" page ... there is no option for restraints, sorry: <https://rbvi.ucsf.edu/chimerax/docs/user/commands/morph.html>
You could try changing any of the parameters that are controlled by the command options described in that page. In my experience, the most useful to try changing is "coreFraction" ... although it is still possible that different options might help for your specific structures.
If changing the command parameter values does not seem to help, the most effective method (but also the most work) is to somehow build more intermediate structures that guide the path. In other words, if your structures are A and B, instead of trying to go in one morph from A->B, manually build one or more intermediate structures A', A'', etc. to guide where you want the morph to go and then do multiple stages of morphing A->A'->A''->B. It is not simple, and may take a lot of your time to build these intermediate structures.
I hope this helps, Elaine ----- Elaine C. Meng, Ph.D. UCSF Chimera(X) team Resource for Biocomputing, Visualization, and Informatics Department of Pharmaceutical Chemistry University of California, San Francisco
On Aug 22, 2024, at 8:07 AM, Enrico Martinez via ChimeraX-users <chimerax-users@cgl.ucsf.edu> wrote:
Dear Chimera-X users!
I try to use the morph command to model the conformational change of GPCR related to its activation.
Having two superimposed conformations of the receptor, which are different in the position of the internal part of the transmembrane helix VI, I try to visualize the displacement of this helix using morph #2,1 frames 250
Unfortunately the produced trajectory looks very unnatural (one helix overlaps with another one).
Would it be possible to improve the accuracy of such morphing e.g. providing some restraints?
Many thanks in advance !
Enrico
Okay, I gotcha, thank you very much Elaine ! Yours sincerely Enrico Il giorno gio 22 ago 2024 alle ore 19:02 Elaine Meng <meng@cgl.ucsf.edu> ha scritto:
Maybe I don't understand your question, but that is exactly what morphing does: it generates intermediate conformers.
However, what I said in my previous reply was that if you want the conformers to be different than the ones you got from morphing, you may have to generate them manually in some kind of multi-step process. This could involve manually rotating bonds, or breaking bonds and moving parts around separately before re-forming bonds. Yes you could do all these steps inside of ChimeraX, but there is no simple way to make ChimeraX do the work for you.
Elaine
On Aug 22, 2024, at 9:21 AM, Enrico Martinez <jmsstarlight@gmail.com> wrote:
Thank you very much Elaine !
Actually I've already tried to increase coreFraction 5-15 or even 50 and it did produce more smooth movement of the helix. BTW, would it be possible to generate several conformers between two extremums using Chimera-x ?
Yours with thanks
Enrico
Il giorno gio 22 ago 2024 alle ore 18:01 Elaine Meng <meng@cgl.ucsf.edu> ha scritto: Hello, All the options are given in the "morph" page ... there is no option for restraints, sorry: <https://rbvi.ucsf.edu/chimerax/docs/user/commands/morph.html>
You could try changing any of the parameters that are controlled by the command options described in that page. In my experience, the most useful to try changing is "coreFraction" ... although it is still possible that different options might help for your specific structures.
If changing the command parameter values does not seem to help, the most effective method (but also the most work) is to somehow build more intermediate structures that guide the path. In other words, if your structures are A and B, instead of trying to go in one morph from A->B, manually build one or more intermediate structures A', A'', etc. to guide where you want the morph to go and then do multiple stages of morphing A->A'->A''->B. It is not simple, and may take a lot of your time to build these intermediate structures.
I hope this helps, Elaine ----- Elaine C. Meng, Ph.D. UCSF Chimera(X) team Resource for Biocomputing, Visualization, and Informatics Department of Pharmaceutical Chemistry University of California, San Francisco
On Aug 22, 2024, at 8:07 AM, Enrico Martinez via ChimeraX-users < chimerax-users@cgl.ucsf.edu> wrote:
Dear Chimera-X users!
I try to use the morph command to model the conformational change of GPCR related to its activation.
Having two superimposed conformations of the receptor, which are different in the position of the internal part of the transmembrane helix VI, I try to visualize the displacement of this helix using morph #2,1 frames 250
Unfortunately the produced trajectory looks very unnatural (one helix overlaps with another one).
Would it be possible to improve the accuracy of such morphing e.g. providing some restraints?
Many thanks in advance !
Enrico
participants (2)
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Elaine Meng -
Enrico Martinez