AlphaFold2 examples from CASP 14: Difference between revisions

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<StructureSection load='' size='350' side='right' caption='' scene='87/875686/Af2_vs_7jx6_chain_a/1'>
<StructureSection load='' size='350' side='right' caption='' scene='87/875686/Af2_vs_7jx6_chain_a/1'>
==Free Modeling Results==
[https://predictioncenter.org/casp14/domains_summary.cgi More than 100 domains] were provided as prediction targets in CASP 14. 14 of these were in the most difficult category, ''free modeling'' ("FM"), meaning that no suitable [[homology modeling]] templates existed. For 8 of these (57%), AlphaFold2's predictions achieve GDT_TS scores of 87-93 (median 88.5). For those 8, GDT_TS of the second best predictions were 43-76 (median 66). Two cases will be analyzed below. First, SARS-CoV-2 ORF8, a 92-residue FM domain where AlphaFold2's GDT_TS was 87, and the second best was 43. Some inspiration for this case came from the discussion by Ribiera<ref name="rubiera">[https://www.blopig.com/blog/2020/12/casp14-what-google-deepminds-alphafold-2-really-achieved-and-what-it-means-for-protein-folding-biology-and-bioinformatics/ CASP14: what Google DeepMind’s AlphaFold 2 really achieved, and what it means for protein folding, biology and bioinformatics], a blog post by Carlos Outeir al Rubiera, December 3, 2020.</ref>.


==SARS-CoV-2 ORF8==
==SARS-CoV-2 ORF8==
Following the discussion by Rubiera<ref name="rubiera">[https://www.blopig.com/blog/2020/12/casp14-what-google-deepminds-alphafold-2-really-achieved-and-what-it-means-for-protein-folding-biology-and-bioinformatics/ CASP14: what Google DeepMind’s AlphaFold 2 really achieved, and what it means for protein folding, biology and bioinformatics], a blog post by Carlos Outeir al Rubiera, December 3, 2020.</ref>,
Our first example is [[SARS-CoV-2 protein ORF8]], a protein that contributes to virulence in COVID-19<ref name="7jtl">PMID: 33361333</ref>. CASP 14 classified ORF8 as a "free modeling" (FM) target<ref name="casp14domains">[https://predictioncenter.org/casp14/domains_summary.cgi Summary and Classifications of Domains for CASP 14].</ref>, meaning that there were no adequate empirical templates for [[homology modeling]]. This was easily confirmed. When the [https://www.uniprot.org/uniprot/P0DTC8 amino acid sequence of ORF8] is submitted to [https://swissmodel.expasy.org/ Swiss Model], it reports the best templates for homology modeling. When the two [[empirical models]] that were not available during CASP 14 are excluded ([[7jtl]] and [[7jx6]]), the best template offered, chain B of [[3afc]], covers only 36% of the length of ORF8 at 13.2% sequence identity, with a 4-residue untemplated gap in the sequence alignment. This template would not be adequate for constructing a useful model.
our first example will be [[SARS-CoV-2 protein ORF8]], a protein that contributes to virulence in COVID-19<ref name="7jtl">PMID: 33361333</ref>. CASP 14 classified ORF8 as a "free modeling" (FM) target<ref name="casp14domains">[https://predictioncenter.org/casp14/domains_summary.cgi Summary and Classifications of Domains for CASP 14].</ref>, meaning that there were no adequate empirical templates for [[homology modeling]]. This was easily confirmed. When the [https://www.uniprot.org/uniprot/P0DTC8 amino acid sequence of ORF8] is submitted to [https://swissmodel.expasy.org/ Swiss Model], it reports the best templates for homology modeling. When the two [[empirical models]] that were not available during CASP 14 are excluded ([[7jtl]] and [[7jx6]]), the best template offered, chain B of [[3afc]], covers only 36% of the length of ORF8 at 13.2% sequence identity, with a 4-residue untemplated gap in the sequence alignment. This template would not be adequate for constructing a useful model.


===X-Ray Structures for ORF8===
===X-Ray Structures for ORF8===
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