RT Journal Article
SR Electronic
T1 The structural coverage of the human proteome before and after AlphaFold
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.08.03.454980
DO 10.1101/2021.08.03.454980
A1 Eduard Porta-Pardo
A1 Victoria Ruiz-Serra
A1 Alfonso Valencia
YR 2021
UL http://biorxiv.org/content/early/2021/08/03/2021.08.03.454980.abstract
AB The protein structure field is experiencing a revolution. From the increased throughput of techniques to determine experimental structures, to developments such as cryo-EM that allow us to find the structures of large protein complexes or, more recently, the development of artificial intelligence tools, such as AlphaFold, that can predict with high accuracy the folding of proteins for which the availability of homology templates is limited.Here we quantify the effect of the recently released AlphaFold database of protein structural models in our knowledge on human proteins. Our results indicate that our current baseline for structural coverage of 47%, considering experimentally-derived or template-based homology models, elevates up to 75% when including AlphaFold’s predictions, reducing the fraction of “dark proteome” from 22% to just 7% and the number of proteins without structural information from 4.832 to just 29.Furthermore, although the coverage of disease-associated genes and mutations was near complete before AlphaFold release (70% of ClinVar’s pathogenic mutations and 74% of oncogenic mutations), AlphaFold models still provide an additional coverage of 2% to 14% of these critically important sets of biomedical genes and mutations. We also provide several examples of disease-associated proteins where AlphaFold provides critical new insights. Overall, our results show that the sequence-structure gap of human proteins has almost disappeared, an outstanding success of direct consequences for the knowledge on the human genome and the derived medical applications.Competing Interest StatementThe authors have declared no competing interest.