[Proteopedia] AlphaFold2 Breakthrough in Protein Structure Prediction

[Eric Martz]

Last month, thanks to some of my colleagues*, I was introduced to the 
breakthrough by AlphaFold2 announced November, 2020.

AlphaFold2 predicted protein structures with truly astonishing accuracy, 
certified by the bi-annual double-blind competition, CASP 14, founded by 
John Moult in the early 1990s. Its predictions were based on the amino 
acid sequences of the target proteins, using massive artificial 
intelligence machine learning from sequence and structure databases. 
Predictions were made "blind", without access to empirical structures of 
the targets, and were judged later in 2020 when empirical structures 
became public. The judges did not know who made which prediction.

AlphaFold2 was one of over 100 groups that submitted predictions for 
over 100 target single-chain domains. In most cases, AlphaFold2 made the 
best prediction, while the second best prediction was far less accurate. 
This was particularly impressive for "free modeling" targets, those for 
which no suitable homology modeling templates were available.

I have briefly summarized the breakthrough here:

https://proteopedia.org/w/Theoretical_modeling#Ab_Initio_Models

I have analyzed two free modeling cases in detail, with interactive 3D 
comparisons. One (92 amino acids) is the ORF8 virulence factor from 
SARS-CoV-2. Among the free modeling targets, it had the largest 
discrepancy between the best and 2nd best predictions. The second is a 
phage RNA polymerase, the longest free-modeling target domain (404 amino 
acids). See:

https://proteopedia.org/w/AlphaFold2_examples_from_CASP_14

I welcome comments, corrections, additions, or feedback!

*Special thanks to my colleagues Roman Sloutsky, Nathaniel Kuzio, Erik 
Nordquist, Can Ozden, Thomas Sawyer, Katie Wahlbeck, Jeanne Hardy, and 
Scott Garman all at UMass Amherst, and Woody Sherman of Silicon 
Therapeutics.

-Eric

Eric Martz, Professor Emeritus, Dept Microbiology (he/him/his)
U Mass, Amherst -- Martz.MolviZ.Org <http://martz.molviz.org/>
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