AlphaFold @ CASP13: “What just happened?”

February 7, 2019

“Let me get the most important question out of the way: is AlphaFold’s advance really significant, or is it more of the same? I would characterize their advance as roughly two CASPs in one (really ~1.8x). Historically progress in CASP has ebbed and flowed, with a ten year period of almost absolute stagnation, finally broken by the advances seen at CASP11 and 12, which were substantial. What we’ve seen this year is roughly twice as much as the recent average rate of advance (measured in mean ΔGDT_TS from CASP10 to CASP12—GDT_TS is a measure of prediction accuracy ranging from 0 to 100, with 100 being perfect.) As I will explain later, there may actually be a good reason for this “two CASPs” effect, in terms of the underlying methodological breakdown. This can be seen not only in the CASP-over-CASP
improvement, but also in terms of the size of the gap between AlphaFold and the second best performer, which is unusually large by CASP standards. Below is a plot that depicts this.”