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.
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.