Protein fold topology search web-server

Question

[johnnytam100]

I'm finding a web server (or standalone program) that allows the upload of a custom PDB for protein fold topology search.

Do you know any of them?

Answer 1

[Wayne]

Did you look at Foldseek webserver? It let's you upload a file.

See more about this offering from the Steinegger Lab here.

The published reference:

van Kempen M, Kim S, Tumescheit C, Mirdita M, Lee J, Gilchrist C, Söding J, and Steinegger. Fast and accurate protein structure search with Foldseek. Nature Biotechnology May 8 2023. https://doi.org/10.1038/s41587-023-01773-0 .

The Foldseek wiki is here.

(For the sake of history, the pre-print reference they were suggesting originally prior to the publication May 8th 2023:
van Kempen M, Kim S, Tumescheit C, Mirdita M, Söding J, and Steinegger M. Foldseek: fast and accurate protein structure search. bioRxiv, doi:10.1101/2022.02.07.479398 (2022).)

[johnnytam100]

Hi Wayne, actually I started off with Foldseek but have a question in mind:

how do I know if I have a novel fold? (because similarity search will often return partially similar hits).

Then, I tried to think of topology, as an illustration:

which simplifies structures to spatial arrangements of secondary structures (or topology).

I want to know if there's any database of protein fold topologies and tools for topology similarity search.

[Wayne]

Mensur added all the traditional ones I meant to add, specifically I was thinking of DALI, CATH and SCOP. Plus, the Conserved Domain Database (CDD). And he mentioned RCSB, specifically, the 'Search' and 'Analyze' dropdowns at RCSB.

If you go to PSBsum you can see topologies as wiring diagrams as you have referenced in your figure of SOD1. They are under the 'Protein' tab for each entry, such as this example for SOD1 at PDBsum.

"PTGLweb is a web server and database of protein structure topologies [Wolf et al., 2020, Bioinformatics; Koch and Schäfer, 2018, Current Opinion in Structural Biology; Schäfer et al., 2015, Bioinformatics]"

From PTGLweb - http://ptgl.uni-frankfurt.de/ :

"This web server allows you to search for protein motifs which can be detected in the graphs"

You may also be interested in http://proteinlego.indirag.org/

The associated publication 'Khan, T., Panday, S.K. and Ghosh, I., 2018. ProLego: tool for extracting and visualizing topological modules in protein structures. BMC bioinformatics, 19(1), p.167.' states:

"Using the topology string, ProLego, compares topology against a non-redundant extensive topology database (ProLegoDB) as well as extracts constituent topological modules. The platform offers interactive topology visualization graphs."

Answer 2

[Mensur Dlakic]

I don't know of a server specifically designed to find new folds. There are many servers for structural analysis and comparison.

• http://ekhidna2.biocenter.helsinki.fi/dali/
• https://www.ebi.ac.uk/msd-srv/ssm/
• http://www.cathdb.info/
• http://prodata.swmed.edu/ecod/
• https://scop.mrc-lmb.cam.ac.uk/
• https://scop.berkeley.edu/
• https://www.rcsb.org/docs/tools/pairwise-structure-alignment

If you can't find a structural match in any of them, either your protein has a novel fold, or a known fold that has been significantly distorted. Partial similarity could happen because there are only so many ways a protein can fold. Like in sequence comparisons, short regions where the match occurs may not be significant enough to consider something related.

By the way, it helps if you spell out exactly what you want and what you tried in the first place, rather than making a single-sentence post.