Table 1.
List of variables.
Fig 1.
Empirical values of Ŝ as a function of S yielded by randomly shuffled 100,000 DCA arrays (blue dots connected by lines), and by 100,000 DCA arrays derived from column-permuted MSAs, where the order of the columns and of the residues within each column were randomly permuted (red triangles connected by lines).
Solid straight lines represents agreement of Ŝ with S, and the dashed curves represent an error range of two standard deviations. Results are shown for six of the domains listed in Table 2, designated by their corresponding pdb identifiers 3fhkF, 1ijxA, 4cmlA, 1olzA, 1k30A, 1wznA, ordered by increasing numbers of sequences in their corresponding MSAs. For 1wxnA, the additional data points (faint red triangles connected by a dashed line) corresponds to an MSA of 5,117 sequences randomly drawn from the original MSA.
Table 2.
S calculated with and without Pb for thirty superfamilies using residue pairwise 3D distances ≤ 5 Å and a minimum of 5 intervening residues.
Table 3.
Wilcoxon Signed Rank 2-tailed tests for the 30 analyses in Table 2.
Fig 2.
S as a function of 3D distance ranges defining distinguished residue pairs.
See discussion in text. A. The s-scores obtained for distance ranges spanning zero to 16 Å. Column pairs corresponding to residue-to-residue distances below the indicated range were excluded from the analysis. B. Detailed plot of the span 2 to 5 Å. Each distance range covers 0.25 Å and is labeled by its upper limit.
Fig 3.
S, SF and PPV scores as a function of various 3D structural coordinates for each of five protein domains.
Structures are ordered by the average of their scores over four methods: CCM (black lines), EVC (cyan lines), GSF (red lines) and PCV (green lines). Below the name for each domain are shown both the mean value of F and of the optimal cut points X for the S-scores. The constant cut point values of x = F × ℓ are shown between the PPV and SF plots. The value of r (the maximum 3D distance defining contacting pairs) is 5 Å.
Fig 4.
Regression analysis of S for 60 Ran GTPase structures versus their crystal structure resolutions.
The coefficient of determination is R2 = 0.00005, indicating that crystal structure resolution fails to explain the variability of S around its mean. The same R4 family MSA and parameters were used here as for the analyses in Table 4.
Fig 5.
Residues in Ran involved in interacting pairs within the transition state structure (pdb: 1k5g) [37].
Sidechains of residues in RanBP1 contacting Ran are labeled in (A) and shown in magenta with dot clouds. The sidechain of Ran Lys130, which plays a role in the stimulation of GTP hydrolysis by RanGAP [37], is indicated. The GTP transition state analog and sidechains of Ran’s catalytic (active site) residues are represented as cyan and red sticks, respectively. A PyMOL session file corresponding to this figure is available at our website. A. Sidechains of residue pairs contributing to the higher S for Ran in the transition state than in the ground state (pdb: 1k5d). These residues are represented as yellow spheres, except for the pivot point residues Phe90 and Val14, which are shown as bright blue spheres, and for two of the unlabeled catalytic residues shown in red (Thr24 and Thr42). B. Ran residues forming pairs whose interactions remain stable over diverse conformational forms (shown as orange and bright blue spheres). These diverse forms include the Ran-RanBP1-RanGAP transition (pdb: 1k5g) and ground (pdb: 1k5d) states; Ran bound to its exchange factor, RCC1 (pdb: 1i2m); Ran bound to GDP (pdb: 3gj0); Ran bound to Ntf1 and GDP (pdb: 1a2k); and Ran bound to RanBP1 and CRM1 (pdb: 4hb2).
Table 4.
S for Ran GTPase in the transition state complexa and in the corresponding ground state complexb.
Table 5.
S as a measure of biological relevance for the N-acetyltransferase Gna1 bound either to coenzyme A (CoA) (pdb: 4ag7; 1.55 Å) or to both CoA and N-acetyl-D-glucosamine-6-phosphate (GlcNAc-6P) (pdb: 4ag9; 1.76 Å).
Table 6.
S as a measure of the overlap between pairs of BPPS pattern residues and the highest DC scoring pairs for the N-acetyltransferase Gna1 bound to both CoA and N-acetyl-D-glucosamine-6-phosphate (GlcNAc-6P) (pdb: 4ag9; 1.76 Å).
Table 7.
S as a measure of structural biological relevance for the bacterial DNA clamp loader complex based on a maximum distance of 2.6 Å.
Table 8.
S as a measure of structural biological relevance for the bacterial DNA clamp loader complex based on a minimum distance of 3 Å and a maximum of 5 Å.