Fig. 1: Generation of a protein foldome for the Flaviviridae.

a, RdRp phylogeny reveals three major lineages within the Flaviviridae: (1) Orthoflavivirus/jingmenvirus (including orthoflavivirus-like—for example, Tamana bat virus); (2) LGF/Pestivirus; and (3) Hepacivirus/Pegivirus. An unrooted tree is shown, with the tombusviruses (TOM) representing the outgroup taxa and a scale bar denoting the number of amino acid substitutions per site. Genome organization is provided for exemplar species, with annotations based on InterProScan searches. b, Crystal structure of DENV-2 NS3 (left) shown alongside a ColabFold predicted structure for the corresponding region of the polyprotein (right). These structures superpose with a root mean square deviation (r.m.s.d.) of 1.6 Å. The predicted structure is colour-coded by per residue confidence scores (predicted local distance difference test (pLDDT)), as indicated in the bar. c, Scatter plot of MSA depth and prediction confidence (pLDDT). d, MSA depths for each sequence block in each genus or subclade, colour-coded as in a (orthoflavivirus-like viruses are included with the orthoflaviviruses). The mean is shown as a solid black line (n = 4,754 (Orthoflavivirus), 704 (jingmenvirus), 4,358 (LGF), 1,278 (Pestivirus), 2,904 (Hepacivirus) and 1,623 (Pegivirus) sequence blocks). e, Scatter plots representing prediction confidence (pLDDT) for ColabFold and ESMFold for each sequence block in each genus or subclade. Numerical values provide the performance ratio between the protein structure prediction methods; values below 1 indicate better performance by ColabFold.