Can AlphaFold be used to complete loops?

[fglaser]

Dear experts,

I wonder if there is a way to use the wonderful power of alphafold just to model missing parts of existing pdbs, e.g. long loops?

I used to use modeller, but it would be great to use alphafold for this taks, specially for long loops.

Thanks! Fabian

[YoshitakaMo]

Hi, @fglaser. Now that colabfold can take --custom-template-path argument to specify a pdb file of interest, now it is possible to complement missing loops.

Here is another example of PDB: 1QG8, which is used as an example in the tutorial of Modeller. https://salilab.org/modeller/wiki/Missing%20residues

To use this feature, please update your localcolabfold first (./update_linux.sh .).

Yoshitaka

[fglaser]

Dear Yoshita,

I did succeed to get a loops recontruction using alphafold as you suggested, but I noticed alphafold also reconstructed the rest of the molecule, not by much but I would prefer only to build the loops without any reconstruction or update of the rest of the molecule, would it be possible?

Why the rest of the molecule is updated or modified too?

I used the following command:

colabfold_batch --amber --num-recycle 3 --num-models 2 --model-order 1,2 --templates --custom-template-path template --msa-mode single_sequence 6vp9_AUX.fasta models_AF_AUX

And the result if you would like to take a looks is the attached model, which has the loops completed, but when if you compare it with the original file (6vp9 chain B) has clear differences.

Thanks!

Fabian

---

Fabian Glaser, PhD

Structural and Computational Biology Unit The Lorry I. Lokey Center for Life Sciences and Engineering Technion - Israel Institute of Technology, Haifa, Israel

On 16 Mar 2022, at 9:22, Yoshitaka Moriwaki @.***> wrote:

Hi, @fglaser https://github.com/fglaser. Now that colabfold can take --custom-template-path argument to specify a pdb file of interest, now it is possible to complement missing loops.

https://user-images.githubusercontent.com/16487484/158537073-50848052-9091-45cd-9247-a530bf93369c.png Here is another example of PDB: 1QG8, which is used as an example in the tutorial of Modeller. https://salilab.org/modeller/wiki/Missing%20residues https://salilab.org/modeller/wiki/Missing%20residues https://user-images.githubusercontent.com/16487484/158536862-5e4b8acd-c3d7-4459-8e54-9a0a696c1d5a.png To use this feature, please update your localcolabfold first (./update_linux.sh .).

Yoshitaka

— Reply to this email directly, view it on GitHub https://github.com/YoshitakaMo/localcolabfold/issues/49#issuecomment-1068813037, or unsubscribe https://github.com/notifications/unsubscribe-auth/ACSBVSGC4RUQVS7ABZ7DUT3VAGD2NANCNFSM5LWJ6UJA. Triage notifications on the go with GitHub Mobile for iOS https://apps.apple.com/app/apple-store/id1477376905?ct=notification-email&mt=8&pt=524675 or Android https://play.google.com/store/apps/details?id=com.github.android&referrer=utm_campaign%3Dnotification-email%26utm_medium%3Demail%26utm_source%3Dgithub. You are receiving this because you were mentioned.

[fglaser]

Thanks a lot!

This is very useful,

Fabian

---

Fabian Glaser, PhD

Structural and Computational Biology Unit The Lorry I. Lokey Center for Life Sciences and Engineering Technion - Israel Institute of Technology, Haifa, Israel

On 16 Mar 2022, at 9:22, Yoshitaka Moriwaki @.***> wrote:

Hi, @fglaser https://github.com/fglaser. Now that colabfold can take --custom-template-path argument to specify a pdb file of interest, now it is possible to complement missing loops.

https://user-images.githubusercontent.com/16487484/158537073-50848052-9091-45cd-9247-a530bf93369c.png Here is another example of PDB: 1QG8, which is used as an example in the tutorial of Modeller. https://salilab.org/modeller/wiki/Missing%20residues https://salilab.org/modeller/wiki/Missing%20residues https://user-images.githubusercontent.com/16487484/158536862-5e4b8acd-c3d7-4459-8e54-9a0a696c1d5a.png To use this feature, please update your localcolabfold first (./update_linux.sh .).

Yoshitaka

— Reply to this email directly, view it on GitHub https://github.com/YoshitakaMo/localcolabfold/issues/49#issuecomment-1068813037, or unsubscribe https://github.com/notifications/unsubscribe-auth/ACSBVSGC4RUQVS7ABZ7DUT3VAGD2NANCNFSM5LWJ6UJA. Triage notifications on the go with GitHub Mobile for iOS https://apps.apple.com/app/apple-store/id1477376905?ct=notification-email&mt=8&pt=524675 or Android https://play.google.com/store/apps/details?id=com.github.android&referrer=utm_campaign%3Dnotification-email%26utm_medium%3Demail%26utm_source%3Dgithub. You are receiving this because you were mentioned.

[AdrienSchahl]

Dear Yoshitaka Morikawi,

I am following this discussion here as I have the same question than @fglaser about rebuilding loops using colabfold : Is there any way to build only missing loops and leave the rest of the protein untouched ? So far I only found a way to do this by extracting the loops created by AF and pasting them in the template, so I wondered if there was any way to do it automatically.

Best,

Adrien Schahl

[camlbrown]

Also commenting to follow the discussion RE loop addition without full model reconstruction

[hima111997]

is there a way to model a missing loop using colabfold leaving the rest of the protein untouched?