Structural Clustering of Transmembrane Domains of Membrane Proteins
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3 days ago
William • 0

I downloaded a bunch of PDB files from http://lmc.uab.cat/TMalphaDB/info.php, where each PDB file contains only the transmembrane helices of the membrane proteins.

I would like to cluster them in terms of their structure, and my first attempt was with Foldseek. The best I could come up with is the follow command:

foldseek easy-multimercluster bundles-alpha/ bundles-alpha-tm50 tmp --multimer-tm-threshold 0.5 --cov-mode 1 --alignment-type 2 --interface-lddt-threshold 0.5 --tmscore-threshold 0.5 --lddt-threshold 0.5

easy-multimercluster is needed because the transmembrane helices are all disconnected. This resulted in some clusters with 4 to 5 members, but mostly singletons.

I tried to look for alternative structure clustering methods, like Secondary Structure Matching (I can only find the webserver PDBeFOLD), but they seem like a great hassle.

Are there any convenient resources for me to cluster the transmembrane domains of membrane proteins, or any suggestions of how I could accomplish this with Foldseek?

foldseek structuralbiology computationalbiology structuralbioinformatics bioinformatics • 3.4k views
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How many is a bunch? Have you checked how similar the clusters/singletons are? I would check them in a visualisation tool like ChimeraX or PyMol. Foldseek is the most appropriate tool I can think of for this use case, so if it's not working it might be a reflection of the data. Another option would be to include more of the proteins so they aren't just disconnected helices to see if that impacts the outcome.

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