[chimerax-users] AlphaFold model for large proteins

[Yunsik Kang]

Thank you Elaine.

This really helps. It seems there is no easy I can run the whole protein. 

Thank you again. This is a great program!

Yk

-----Original Message-----
From: Elaine Meng <meng at cgl.ucsf.edu> 
Sent: Thursday, September 9, 2021 4:54 PM
To: Yunsik Kang <kangy at ohsu.edu>
Cc: ChimeraX Users Help <chimerax-users at cgl.ucsf.edu>
Subject: [EXTERNAL] Re: [chimerax-users] AlphaFold model for large proteins

It's important to remember that the red-to-orange parts have low confidence scores and "should not be interpreted" so it is not meaningful whether or not they are clashing.  See:

<https://rbvi.ucsf.edu/chimerax/docs/user/tools/alphafold.html#coloring>

Elaine
 
> On Sep 9, 2021, at 3:39 PM, Yunsik Kang via ChimeraX-users <chimerax-users at cgl.ucsf.edu> wrote:
> 
> Hi Tom,
>  
> Thank you so much! It is great that I inspired you to write this command.
>  
> Since I have you (and I am no expert in structural biology), do you think alphafold will soon update larger proteins? Is there still a limitation? On your Youtube videos you guys state after 700 aa the system crashes a lot.
>  
> If I know a protein that perhaps might have a similar structure to my protein would it help resolves these clashing problems?
>  
> As you can see I tried to hide what my protein of interest was but it seems there are not a lot of 5005 amino acid proteins =).
>  
> Thank you again!
> Yunsik
>  
>  
> From: Tom Goddard <goddard at sonic.net> 
> Sent: Thursday, September 9, 2021 3:17 PM
> To: Yunsik Kang <kangy at ohsu.edu>
> Cc: ChimeraX Users Help <chimerax-users at cgl.ucsf.edu>
> Subject: [EXTERNAL] AlphaFold model for large proteins
>  
> Hi Yunsik, 
>  
>   Inspired by your question and Tristan Croll's comment that the AlphaFold database has human proteins longer than 1400 amino acids computed as separate 1400 amino acid chunks I made a ChimeraX command "bigalpha" that loads and aligns these chunks.
>  
> https://rbvi.github.io/chimerax-recipes/big_alphafold/bigalpha.html
>  
> I attach two images and a PDB model made by running that command in ChimeraX for 5005 amino acid transmembrane protein
>  
> Q2LD37 | K1109_HUMAN Transmembrane protein KIAA1109 OS=Homo sapiens OX=9606 GN=KIAA1109 PE=1 SV=2
>  
> and also here are a few other examples I looked at yesterday.
>  
> https://twitter.com/UCSFChimeraX/status/1435870388043411458
>  
> https://twitter.com/UCSFChimeraX/status/1435760774824169474
>  
> https://twitter.com/UCSFChimeraX/status/1435859111053193216
>  
> Keep in mind that the pieces of these models are not aligned in a reliable way and probably clash badly with each other because AlphaFold did not compute them as part of one structure.  So these structures should only give you a very rough idea about the protein.
>  
>   Tom
>  
> This is the confidence coloring determined by AlphaFold, red low, blue high confidence.  To reproduce this color using ChimeraX daily build open the PDB model and type command "color bfactor #1 palette alphafold".  (The confidence value is saved as the bfactor in the PDB file).
> <image001.png>
>  
> Different AlphaFold chunks have different colors and chain identifiers in the PDB model.
> <image002.png>
>  
> 
> 
> On Sep 8, 2021, at 2:45 PM, Yunsik Kang via ChimeraX-users <chimerax-users at cgl.ucsf.edu> wrote:
>  
> Hello,
>  
> My name is Yunsik Kang, and I am a postdoc in Marc Freeman’s lab at the Vollum Institute.
>  
> I would love to use ChimeraX to predict the structure of my protein of interest. I watched all the YouTube videos and tried to run the program.
>  
> Unfortunately, my protein is 5005 amino acids in humans and 2958 aa in yeast. I get a message “Please use the full AlphaFold system for long sequences.”
>  
> My question is what is the best way to approach this problem? Should I cut the protein in half and run the program? In one of the videos, it mentions after 700 aa it will have problems. Will it work if I get Colab-Pro? Or would the server crash no matter what.
>  
> I am not a structural biologist, but I hope the structure can help be predict me with my research.  
>  
> Thank you,
> Yunsik
>  
>  
> _______________________________________________
> ChimeraX-users mailing list
> ChimeraX-users at cgl.ucsf.edu
> Manage subscription:
> https://www.rbvi.ucsf.edu/mailman/listinfo/chimerax-users
>  
> _______________________________________________
> ChimeraX-users mailing list
> ChimeraX-users at cgl.ucsf.edu
> Manage subscription:
> https://www.rbvi.ucsf.edu/mailman/listinfo/chimerax-users