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/AlphaFold2.ipynb

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/AlphaFold2.ipynb#custom_templates

  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
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