Senior_et_al-2019-Proteins__Structure,_Function,_and_Bioinformatics.pdf (2.37 MB)

Protein structure prediction using multiple deep neural networks in the 13th Critical Assessment of Protein Structure Prediction (CASP13).

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journal contribution
posted on 17.01.2020 by Andrew W Senior, Richard Evans, John Jumper, James Kirkpatrick, Laurent Sifre, Tim Green, Chongli Qin, Augustin Žídek, Alexander WR Nelson, Alex Bridgland, Hugo Penedones, Stig Petersen, Karen Simonyan, Steve Crossan, Pushmeet Kohli, David T Jones, David Silver, Koray Kavukcuoglu, Demis Hassabis
We describe AlphaFold, the protein structure prediction system that was entered by the group A7D in CASP13 Submissions were made by three free-modelling methods which combine the predictions of three neural networks. All three systems were guided by predictions of distances between pairs of residues produced by a neural network. Two systems assembled fragments produced by a generative neural network, one using scores from a network trained to regress GDT_TS. The third system shows that simple gradient descent on a properly constructed potential is able to perform on-par with more expensive traditional search techniques and without requiring domain segmentation. In the CASP13 free-modelling assessors' ranking by summed z-scores, this system scored highest with 68.3 vs 48.2 for the next closest group. (An average GDT_TS of 61.4.) The system produced high-accuracy structures (with GDT_TS scores of 70 or higher) for 11 out of 43 free-modelling domains. Despite not explicitly using template information, the results in the template category were comparable to the best performing template-based methods. This article is protected by copyright. All rights reserved.