I have a question that’s unrelated to the article you might be able to answer…is it viable to use something like alphafold to predict whether a protein variant is folding the same way as the wild type or would you always need to validate that with imagery?
AlphaFold is a real game-changer in predicting many protein structures, but its precision in dealing with single residue mutations, particularly in non-standard proteins, isn't a sure bet.
The tool excels because it's been trained on a massive database of known protein structures. It's great at making educated guesses based on that data, but it's not as reliable when it comes to variations that don't have much historical data, like specific mutations at the residue level.
For these finer details, traditional physics-based methods, like molecular dynamics simulations, might offer more insight. They really get into the atomic-level interactions, which can be critical for understanding the subtle effects of amino acid changes.
AlphaFold is likely to identify significant structural changes, but it might not be your go-to for pinpointing smaller, more nuanced shifts.
AlphaFold is basically a pattern matching program on steroids. Don't get me wrong, it's incredible, but if there's not experimental data somewhat describing what that variant would look like, AlphaFold is liable to just make spaghetti out of it.
Ugh...ok so not reliable to drive experimental follow ups it seems.
What would it cost to image a certain protein if I sent you the mutant cell lines roughly? I've got 4 mutants whose structure I'm interested in looking at. I can get into more details but essentially, what I'm trying to figure out is if a truncated version of this protein can be created that would expose all the right binding sites and maybe fold somewhat correctly in order to be delivery via AAV for gene therapy.
The mutants I want to look at aren't the truncated protein but the actual diseased types and if I saw structural problems in them, I might assume that fixing said structure could restore function.
Send me an email to the one in my profile - I'd be happy to chat a bit. Not sure a structure is the best way to get the information you're looking for.
