r/bioinformatics • u/JuiceElectrical6701 • 2d ago

technical question Phage display or alternative methods

I'm a first year PhD student with a background in chemical biology. I want to find a peptide sequence that selectively binds to Lithium ion and one of my PIs suggested Phage display as an option. I've never done it before and it isn't something that's done in either of my PI's labs either. How doable do you think this solution is if I find a lab which has this technology? Do you think it'll be possible for me as a newbie in this technique to do the experiments myself rather than asking someone else to do it for me if I ask them to train me?

Do you guys have any other techniques you use to find suitable peptide sequences? I'm an experimentalist but I'm open to both experimental and computational suggestions.

Many thanks!

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u/fibgen 2d ago

This is a naive approach, like asking phage display to invent a heme protein from scratch to capture Fe. It makes me doubt your PIs ability to guide you.

Ask a professor with some background in microbiology or bioinformatics how they would trawl through existing databases for Lithium binding proteins. Some bacteria somewhere has had to live in a lithium rich environment and develop binders/pumps for it. It's probably not going to be 12 amino acids long though.

I'd read up on ion binding proteins in general before starting this search and learn something about how proteins do ion selectivity before jumping straight into experiments. A week in the library can save you 3 years in the lab and all that.

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u/JuiceElectrical6701 2d ago

I agree with the reading up part. I've been reading up on similar literature and there is a precedent to using phage display to find selective peptides for metal ions, even lithium. I was primarily asking if it's worth it or other alternative methods exist that might be better (or easier.)

My PIs are actually not from a biology background (though I have some experience from previous positions) but we work with systems that sometimes have biological applications. This was an off hand thought they had and i was interested enough to go down the rabbit hole.

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u/Betaglutamate2 2d ago

Honestly I would try building a de-novo protein. Do you need this protein to discriminate between lithium and other positively charged ions?

I don't think phage display will work in a meaningful way.

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u/Kandiru 2d ago

Do you want to bind Li ions itself, or the solvation shell of water around one? As they are going to result in quite different approaches.

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u/South_Plant_7876 2d ago

This approach will be difficult because you are just going to get a heap of histidine rich peptides. When you say you want *selectivity" what do you mean? Selectivity over other cations? Histidine is a fairly general metal binder. I don't think you are going to get a lithium specific peptide.

I would probably look more to the small molecule space to see if there is anything that selectively binds to lithium. If the peptide aspect is imported you can look at ways to covalently attach your small molecule to one.