[chimerax-users] Could you please inform the best advice to solve a structure via colabfold when GPU is an issue? I tried some routes already.

[Elaine Meng]

Hi Josh,
I'm no expert in this area but here are a few thoughts:

(1) make sure that your protein is not already available in the AlphaFold Database, e.g. did you try the Fetch option on the tool?
<https://rbvi.ucsf.edu/chimerax/docs/user/tools/alphafold.html#match>

(2) for parameter settings, you might consider asking the ColabFold developers (see authors on the ColabFold publication in the ChimeraX AlphaFold documentation), 
<https://rbvi.ucsf.edu/chimerax/docs/user/tools/alphafold.html#predict>

...but perhaps some of these parameters are not adjustable via the ChimeraX tool.  If so, you'd need to run ColabFold directly instead.  I don't know if the UCSF professor you're collaborating with is in one of the groups with access to the UCSF Wynton cluster, but there is information about setup and running on the Wynton cluster here:
<https://www.rbvi.ucsf.edu/chimerax/data/singularity-apr2022/afsingularity.html>

(3) as mentioned in the ChimeraX AlphaFold documentation (top link above), you can pay Google for Colab accounts that provide greater computing resources.  Sounds like you already tried that, but with high predicted error.  It is unclear, however, whether this structure would have high predicted error regardless of whether you solved it in multiple pieces or a single piece.  Some proteins may simply have lots of disordered/unstructured regions, and/or maybe there is not much sequence data available for homologs of this protein to help constrain the problem.

(4) consider trying ESMFold, for which there is also a tool in ChimeraX analogous to the AlphaFold one.  There are database fetch and new-prediction options.  Still, I don't know if this approach would work in your specific case either.
<https://rbvi.ucsf.edu/chimerax/docs/user/tools/esmfold.html>

I hope this helps,
Elaine
-----
Elaine C. Meng, Ph.D.                       
UCSF Chimera(X) team
Department of Pharmaceutical Chemistry
University of California, San Francisco

> On Apr 14, 2023, at 2:52 PM, Josh Gutierrez via ChimeraX-users <chimerax-users at cgl.ucsf.edu> wrote:
> 
> Hello, 
> 
> I recently submitted a job through ChimeriaX and used the "prediction" task for it to be solved via Alphafold2-- the sequence is about 1300 amino acids in length. However, the protein could not be solved by alphafold2 and the colabfold reports the GPU consumption is too high for the structure to be solved. To resolve the problem, I tried breaking the sequence into two to solve this expected bimodal protein individually (into two separate structural parts) and even in combination purchased "compute units" for more memory and storage to do this, but the structure can't be solved without high predicted error. 
> 
> Please let me know what you think may  resolve this issue. Currently, I am working with an external professor who may be able to connect me with a collaborator on this issue at UCSF if there is a cluster or core we can use to expedite the process to solve this structure I am addressing. Please let me know your thoughts at your earliest convenience. Please also let me know if you need any more information!  
> 
> Many thanks, 
> Josh Gutierrez