Ready to be a protein structure sleuth? Can you guess the identity of this protein?? Based on your analysis, which structural model would you select?

Protein structure prediction tools, like AlphaFold2, are incredibly helpful in bridging our understanding of protein structure, but they're most useful in the context in which they're trained.

AlphaFold2 was trained on experimentally determined protein structure and protein sequence databases. This means AlphaFold2 can be great for predicting structures for proteins where experimental structural information exists in some form (i.e. for homologs or related domain families), but it can struggle with proteins where traditional experimental methods have failed (i.e. regions with high disorder). Of particular note here, AlphaFold2 doesn't recognize the membrane plane so structure predictions for transmembrane proteins require careful interpretation.

So keep the corresponding biology and protein function front and center as you evaluate these models - ready, set, go!