LazyAF, a pipeline for accessible medium-scale in silico prediction of protein-protein interactions

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Abstract

Artificial intelligence has revolutionized the field of protein structure prediction. However, with more powerful and complex software being developed, it is accessibility and ease of use rather than capability that is quickly becoming a limiting factor to end users. Here, I present a Google Colaboratory-based pipeline, named LazyAF, which integrates the existing ColabFold BATCH to streamline the process of medium-scale protein-protein interaction prediction. I apply LazyAF to predict the interactome of the 76 proteins encoded on a broad-host-range multi-drug resistance plasmid RK2, demonstrating the ease and accessibility the pipeline provides.

Availability

LazyAF is freely available at https://github.com/ThomasCMcLean/LazyAF

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  1. Absolutely. If you have a few in mind for one complex i would just put that all into the original ColabFold as a single job, otherwise I would use the results from an in silico pulldown to guage what might be forming a complex using a networking tool such as cytoscape and then go from there

  2. It can but currently this requires doing each bait seperately. e.g. protein A vs. list A then protein B vs. list A and on. The main limiting factor is the computing time and cost in Part 2

  3. Here, I present a Google Colaboratory-based pipeline, named LazyAF, which integrates the existing ColabFold BATCH to streamline the process of medium-scale protein-protein interaction prediction.

    Thanks so much for sharing this tool! I really enjoyed reading about it and can't wait to try it myself.

  4. Figure 3.

    You mentioned that several of the top predicted PPIs have been previously experimentally validated. It would be interesting to know which of these annotations predicted by your pipeline are supported by experimental validation. Could you somehow denote this in this figure?

  5. uggesting that a score of co-folding between protein A (bait):protein B (candidate) sometimes is different from that of a co-folding between protein B (bait):protein A (candidate).

    If you run the analysis multiple times, do you see variation between runs or is it only when you switch the chains?

  6. the sequence of the ‘bait’ and that of a ‘candidate’ joined via a colon.

    I'm curious if you're pipeline supports more than 2 proteins. For example, could I put in a handful of proteins to see if they form a complex?

  7. a ‘bait’ protein

    I think based on your analysis that the answer to this question is yes, but can you do multiple bait proteins as well as multiple candidate proteins? Also curious about how many proteins this can handle?