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Creating the largest protein-protein interaction dataset in the world
4.6k words, 22 minute reading time
You’ll probably need to re-run Alphafold2 with dozens of different seeds, maybe do MSA subsampling, and a laundry list of other ‘hacks’ to get these models to give a somewhat correct structure and, thus, a proxy for binding affinity. Atom-sized deviations can cause catastrophic failures in predicted final structures, conformational flexibility can lead to unpredictable binding modes, and the sheer number of potential interaction surfaces explodes combinatorially. I intuitively get the sense that AlphaSeq is a fair bit more accurate than Y2H, given how terrible Y2H is, and easier to set up than Yeast Display, since purified protein isn’t needed, so that’s a win in of itself!
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