Table 2.
Comparison of fold recognition and Rosetta models for large protein families
| Known function | Rc | TMscore | ||||||
|---|---|---|---|---|---|---|---|---|
| Name | #seq | Ev | HH | SP | M | M_HH | M_SP | HH_SP |
| WECH: O-acetyltransferase (YiaH) | 24,750 | −2.4 | 0.0 | 0.1 | 0.9 | 0.1 | 0.2 | 0.1 |
| SATP: Succinate-acetateproton symporter (YaaH) | 2298 | −2.1 | 0.4 | 0.5 | 1.1 | 0.3 | 0.3 | 0.8 |
| LSPA: Lipoprotein signal peptidase | 8156 | −2.0 | 0.2 | 0.1 | 1.0 | 0.2 | 0.3 | 0.3 |
| YADH: ABC-type multidrug transport permease | 42,626 | −2.0 | 0.1 | 0.1 | 0.7 | 0.3 | 0.2 | 0.2 |
| YEBZ: Putative copper export protein | 4067 | −2.0 | 0.1 | 0.1 | 0.8 | 0.2 | 0.3 | 0.2 |
| CRCB: Fluoride ion exporter | 7829 | −1.8 | 0.2 | 0.3 | 1.0 | 0.2 | 0.2 | 0.3 |
| LPTG: Lipopolysaccharide export system permease | 8101 | −1.8 | 0.0 | 0.1 | 0.9 | 0.1 | 0.1 | 0.2 |
| FTSW: Lipid II flippase | 14,900 | −1.7 | 0.0 | 0.1 | 1.0 | 0.1 | 0.2 | 0.2 |
| RFAL: O-antigen ligase | 13,535 | −1.7 | 0.2 | 0.1 | 0.9 | 0.3 | 0.2 | 0.2 |
| CCMB: Heme exporter protein B | 2433 | −1.6 | 0.1 | 0.1 | 0.7 | 0.2 | 0.2 | 0.2 |
| MLAE: ABC transporter permease for lipid asymmetry | 7662 | −1.4 | 0.0 | 0.1 | 0.9 | 0.1 | 0.2 | 0.3 |
| SULP: Sulfate permease | 6647 | −1.2 | 0.1 | 0.0 | 0.8 | 0.2 | 0.2 | 0.2 |
| TOLQ: Biopolymer transport protein | 9256 | −1.2 | 0.1 | 0.1 | 0.7 | 0.2 | 0.2 | 0.2 |
| LGT: Prolipoprotein diacylglyceryl transferase | 8121 | −1.1 | 0.1 | 0.2 | 1.0 | 0.2 | 0.3 | 0.3 |
| Q97UR7: N-methylhydantoinase B (HyuB-3) | 4491 | −1.0 | 0.1 | 0.1 | 1.1 | 0.1 | 0.1 | 0.1 |
| YGAZ: putative L-valine exporter | 6435 | −1.0 | 0.1 | 0.2 | 0.9 | 0.2 | 0.3 | 0.2 |
| CCMC: Heme exporter protein C | 5965 | −0.8 | 0.1 | 0.1 | 1.1 | 0.2 | 0.2 | 0.2 |
| YEDZ: Sulfoxide reductase heme-binding subunit | 2247 | −0.7 | 0.2 | 0.2 | 1.0 | 0.2 | 0.3 | 0.3 |
| YIAM: TRAP transporter small permease protein | 10,715 | −0.7 | 0.1 | 0.2 | 1.1 | 0.3 | 0.3 | 0.2 |
| TTDA: Tartrate dehydratase, alpha subunit | 4238 | −0.6 | 0.0 | 0.1 | 1.2 | 0.1 | 0.1 | 0.1 |
| UPPP: Undecaprenyl pyrophosphate phosphatase | 7842 | −0.6 | 0.0 | 0.1 | 1.0 | 0.2 | 0.2 | 0.2 |
| PLSY: Probable glycerol-3-phosphate acyltransferase | 6112 | −0.4 | 0.1 | 0.2 | 1.1 | 0.2 | 0.4 | 0.2 |
| FLIL: Flagellar protein | 2690 | −0.3 | 0.7 | 0.5 | 0.8 | 0.5 | 0.4 | 0.9 |
| CYDB: Cytochrome bd oxidase 2 | 6864 | 0.0 | 0.1 | 0.1 | 1.0 | 0.2 | 0.2 | 0.1 |
| CYDA: Cytochrome bd oxidase 1 | 6200 | 0.1 | 0.0 | 0.1 | 1.2 | 0.1 | 0.2 | 0.2 |
| MOTA: Motility protein A, flagellar motor proton conductor | 4734 | 0.3 | 0.1 | 0.1 | 0.9 | 0.1 | 0.1 | 0.2 |
| SLYB: Outer membrane lipoprotein | 1860 | 0.3 | 0.1 | 0.2 | 0.8 | 0.2 | 0.2 | 0.1 |
| MRED: Rod shape-determining protein | 1546 | 0.6 | 0.5 | 0.5 | 0.8 | 0.5 | 0.4 | 0.6 |
| ZUPT: Zinc transporter | 10,517 | 0.6 | 0.1 | 0.1 | 0.8 | 0.2 | 0.1 | 0.2 |
| YOHK: Putative effector of murein hydrolase LrgB | 3941 | 2.3 | 0.2 | 0.1 | 0.9 | 0.4 | 0.2 | 0.2 |
| PRSW: Membrane proteinase | 2500 | 5.3 | 0.2 | 0.2 | 0.9 | 0.3 | 0.3 | 0.7 |
| DDG: Lipid A biosynthesis palmitoleoyl acyltransferase | 9430 | 5.8 | 0.4 | 0.1 | 1.0 | 0.4 | 0.2 | 0.2 |
| Unknown function | Rc | TMscore | ||||||
|---|---|---|---|---|---|---|---|---|
| Name | #seq | Ev | HH | SP | M | M_HH | M_SP | HH_SP |
| YQFA: UPF0073 inner membrane protein | 7596 | −2.6 | 0.1 | 0.4 | 1.1 | 0.2 | 0.5 | 0.3 |
| YCED: Uncharacterized protein | 1604 | −2.5 | 0.1 | 0.2 | 0.9 | 0.2 | 0.2 | 0.2 |
| YPHA: Inner membrane protein | 2986 | −2.2 | 0.1 | 0.4 | 1.0 | 0.2 | 0.3 | 0.2 |
| YADS: UPF0126 inner membrane protein | 5222 | −1.9 | 0.1 | 0.1 | 0.9 | 0.2 | 0.3 | 0.2 |
| YHHN: Uncharacterized membrane protein | 2529 | −1.9 | 0.1 | 0.2 | 0.9 | 0.2 | 0.3 | 0.2 |
| YIDH: Inner membrane protein | 1041 | −1.9 | 0.1 | 0.2 | 0.6 | 0.3 | 0.3 | 0.2 |
| YITE: UPF0750 membrane protein | 8326 | −1.7 | 0.1 | 0.1 | 0.9 | 0.2 | 0.3 | 0.3 |
| HDED: Acid resistance membrane protein | 2885 | −0.6 | 0.1 | 0.2 | 0.8 | 0.2 | 0.2 | 0.2 |
| YFIP: DTW domain-containing protein | 3100 | −1.5 | 0.2 | 0.2 | 0.9 | 0.2 | 0.2 | 0.1 |
| YPJD: ABC-type uncharacterized permease | 6180 | −1.4 | 0.2 | 0.2 | 0.9 | 0.2 | 0.3 | 0.2 |
| YJFL: UPF0719 inner membrane protein | 1581 | −1.3 | 0.1 | 0.1 | 0.7 | 0.2 | 0.3 | 0.3 |
| YTEJ: Uncharacterized membrane protein | 5733 | −1.2 | 0.1 | 0.1 | 1.0 | 0.2 | 0.2 | 0.2 |
| YIHY: UPF0761 membrane protein | 10,144 | −0.9 | 0.1 | 0.1 | 0.9 | 0.1 | 0.2 | 0.2 |
| YQAA: Inner membrane protein | 2187 | −0.9 | 0.1 | 0.3 | 1.0 | 0.2 | 0.4 | 0.3 |
| YHID: Uncharacterized protein | 4416 | −0.7 | 0.2 | 0.2 | 1.0 | 0.2 | 0.1 | 0.2 |
| YLOU: Uncharacterized protein | 3738 | −0.7 | 0.4 | 0.5 | 0.9 | 0.3 | 0.3 | 0.8 |
| YGDD: UPF0382 inner membrane protein | 3025 | −0.6 | 0.5 | 0.3 | 1.0 | 0.3 | 0.2 | 0.4 |
| YJCH: Inner membrane protein | 1307 | −0.5 | 0.3 | 0.2 | 0.8 | 0.4 | 0.2 | 0.2 |
| YFCA: UPF0721 transmembrane protein | 18,846 | 0.0 | 0.1 | 0.1 | 1.0 | 0.2 | 0.3 | 0.2 |
| YOHJ: Putative effector of murein hydrolase | 3608 | 0.4 | 0.2 | 0.3 | 0.5 | 0.3 | 0.4 | 0.6 |
| YHHQ: Inner membrane protein | 3398 | 0.7 | 0.4 | 0.2 | 1.0 | 0.4 | 0.3 | 0.2 |
| YAII: UPF0178 protein | 3144 | 0.8 | 0.6 | 0.7 | 1.1 | 0.5 | 0.5 | 0.4 |
| YUXK: Predicted thiol-disulfide oxidoreductase | 1881 | 1.3 | 0.3 | 0.3 | 1.1 | 0.3 | 0.3 | 0.5 |
| YICC: UPF0701 protein | 4293 | 1.5 | 0.1 | 0.1 | 1.0 | 0.1 | 0.1 | 0.1 |
| YEIH: UPF0324 inner membrane protein | 4863 | 4.2 | 0.3 | 0.2 | 0.9 | 0.4 | 0.5 | 0.7 |
| RARD: Putative chloramphenical resistance permease | 74,507 | 6.3 | 0.1 | 0.1 | 1.0 | 0.3 | 0.3 | 0.2 |
Column 2: number of unique proteins in family; Column 3: negative log10 of E-value of top match found in HHsearch profile–profile search of PDB; Columns 4–6: fit to predicted contacts (Rc value) of best fitting of top 10 HHsearch hits (column 4), of best fitting of top 10 SPARKS-X hits (column 5), and Rosetta model (column 6). Native structures have Rc values ranging from 0.7 to 1.2 (Figure 17). Columns 7–9: structural similarity (TMscore) between Rosetta model (M) and best fitting HHsearch model, between Rosetta model and best fitting SPARKS-X model, and between best fitting HHsearch and SPARKS-X models. The Rosetta models fit the contacts as well as expected for native structures and are very different from best fitting HHsearch and SPARKS-X models. For RARD and YEIH, the HHsearch E-value is less than 1E-04, the recommended threshold for inclusion in the same Pfam clan (Xu and Dunbrack, 2012), but the fit with the co-evolutionary contacts was very poor (Rc < 0.3); these two cases are discussed in sections below. For FLIL and YAII, the Rc values for very weak HHSearch and SPARKS-X hits (E-values worse than 0.1) are greater than 0.6 but the contacts constrain only a portion of the structure.