Re: [Chimera-users] Chimera-X inteprhase of the AlphaFold
Hi Enrico, The ChimeraX AlphaFold interface does not allow specifying your own structure template. But the ColabFold web server does allow this https://colab.research.google.com/github/sokrypton/ColabFold/blob/main/Alpha... using "template mode: custom" on that web page and follow instructions they list on that page for using custom templates https://colab.research.google.com/github/sokrypton/ColabFold/blob/main/Alpha... I have tried custom templates with AlphaFold in the past and it has never changed the predicted structure. AlphaFold only uses the template as a first guess at the structure then it does multiple rounds (by default 3 recycles) of creating new models. If AlphaFold is pretty confident about a different conformation than the template it simply replaces the starting structure with the conformation it prefers. Possibly if AlphaFold has low confidence in a prediction a template could bias it to get a different conformation but I've never seen that happen. This is a basic limitation of AlphaFold that it is not designed to optimize an existing structure. The input that dominates the calculation is the sequence and the deep sequence alignment that it computes, not template structures. Possibly AlphaFold could be prodded to predict different conformations by changing the deep sequence alignment to include just the sequences known to fold in the desired conformation and excluding sequences known to fold in a different conformation. Tom
On Jul 13, 2023, at 3:43 AM, Enrico Martinez via Chimera-users <chimera-users@cgl.ucsf.edu> wrote:
Dear Chimera-X users!
In parallel to the modeller, I am trying to use the Alpha fold interface with the aim to full model starting from the sequence using template.
The problem is that I can not define manually which template I would like to use for each prediction so the interphase takes its automatically based on the input sequence and the final prediction is not very precise. Would it be possible rather to specify a specific pdb ID additionally to a given sequence ?
Many thanks in advance
Enrico _______________________________________________ Chimera-users mailing list -- chimera-users@cgl.ucsf.edu To unsubscribe send an email to chimera-users-leave@cgl.ucsf.edu Archives: https://mail.cgl.ucsf.edu/mailman/archives/list/chimera-users@cgl.ucsf.edu/
Hello, If you want a model specifically based on a certain template, try the Modeller Comparative tool instead. Details of how to use it are in the help page: <https://rbvi.ucsf.edu/chimerax/docs/user/tools/modeller.html> ...but here's a possible outline: (1) open the template structure (2) open the sequence of the target. If you have a sequence file (e.g. FASTA) you can open that. Or, go to the uniprot website to figure out the sequence ID that you need. E.g. to open uniprot sequence LDLR_HUMAN in ChimeraX, command: open uniprot:LDLR_HUMAN (3) associate the template structure with the target sequence, even though it is different from the sequence of the template structure. Association and how to do it: <https://rbvi.ucsf.edu/chimerax/docs/user/tools/sequenceviewer.html#associati... (4) start Modeller Comparative from the main Tools menu or the Tools menu of the sequence-window context menu #3 should work fine if the sequences are reasonably similar. If the sequences are quite different (too difficult for ChimeraX to associate correctly), you may need to make an alignment of the two sequences using some other program. Then open that sequence alignment file instead of the single sequence. Associate the template structure with its own sequence. Then proceed with #4 above. I hope this helps, Elaine ----- Elaine C. Meng, Ph.D. UCSF Chimera(X) team Department of Pharmaceutical Chemistry University of California, San Francisco
I gotcha thank you very much for these useful tips! I am going to check the modeller interphase asap. Yours with thanks Enrico Il giorno ven 14 lug 2023 alle ore 00:09 Elaine Meng <meng@cgl.ucsf.edu> ha scritto:
Hello, If you want a model specifically based on a certain template, try the Modeller Comparative tool instead. Details of how to use it are in the help page: <https://rbvi.ucsf.edu/chimerax/docs/user/tools/modeller.html>
...but here's a possible outline:
(1) open the template structure
(2) open the sequence of the target. If you have a sequence file (e.g. FASTA) you can open that. Or, go to the uniprot website to figure out the sequence ID that you need. E.g. to open uniprot sequence LDLR_HUMAN in ChimeraX, command: open uniprot:LDLR_HUMAN
(3) associate the template structure with the target sequence, even though it is different from the sequence of the template structure. Association and how to do it: <https://rbvi.ucsf.edu/chimerax/docs/user/tools/sequenceviewer.html#associati...
(4) start Modeller Comparative from the main Tools menu or the Tools menu of the sequence-window context menu
#3 should work fine if the sequences are reasonably similar. If the sequences are quite different (too difficult for ChimeraX to associate correctly), you may need to make an alignment of the two sequences using some other program. Then open that sequence alignment file instead of the single sequence. Associate the template structure with its own sequence. Then proceed with #4 above.
I hope this helps, Elaine ----- Elaine C. Meng, Ph.D. UCSF Chimera(X) team Department of Pharmaceutical Chemistry University of California, San Francisco
participants (3)
-
Elaine Meng -
Enrico Martinez -
Tom Goddard