(A) Multiple sequence alignment. (B) Evolutionary coupling (EC) analysis. (C–D) Calculation of the EC values between residues in allosteric and orthosteric pockets. (E) Pairwise compared the …
(A) The sequence lengths of all proteins in our data set. (B) The number of homologous sequences. Neff represents the number of effective homologous sequences obtained under 80% reweighting. (C) …
Raw data for Figure 2.
(A) Prediction accuracy of using different numbers of residue pairs. We defined that the criterion for successful prediction is that the Z-score of the allosteric pocket is greater than 0.5. (B) The …
Raw data for Figure 2—figure supplement 2.
Two residues that are not part of the orthosteric and allosteric sites were randomly selected from the surface residues of proteins. Among them, one was taken as the first center, and the residues …
Raw data for Figure 2—figure supplement 3.
Number of residues refers to the number of residues from allosteric pockets, including the number of all residues in allosteric pockets and predicted key allo-residues.
Raw data for Figure 3.
Raw data for Figure 3—figure supplement 1.
These three distributions are the distributions of the statistics in BCR-ABL1, Tar, and PDZ3.
For each of the seven proteins, we randomly sampled different numbers of homologous sequences such as 1 L, 2 L, and so on. The ratio refers to the proportion of identical key allo-residues …
Raw data for Figure 3—figure supplement 3.
(A) The crystal structure of the kinase domain of BCR-ABL1. The allosteric inhibitor asciminib, represented by sticks, binds to the myristoyl pocket (marine). (B) Predicted key allo-residues in the …
Raw data for Figure 4.
(A) The crystal structure of holo-Tar. Aspartate (Asp) is represented by magenta sticks, the allosteric pocket is represented by marine surface, and the salmon helix is selected as the orthosteric …
Raw data for Figure 5.
(A) KeyAlloSite predicted key allo-residues for Candida antarctica lipase B. Among the predicted residues, the residues that have been annotated by the literature are shown as marine spheres, and …
Raw data for Figure 6.
Protein | Gene | Predicted key allo-residues | Mutation* | Cancer type† |
---|---|---|---|---|
AR1 | AR | D732 | D732N | SKCM |
AR2 | AR | M832 | M832I | SKCM |
PTP-1B | PTPN1 | M282 | M282T | COAD |
CDK2 | CDK2 | P155 | P155H | UCEC |
CK2alpha | CSNK2A1 | F54; A110 | F54C; A110T | UCEC; UCEC, GBM |
MAPK14 | MAPK14 | P191; E192 | P191S; P191H; E192Q | SKCM; KIRC; BLCA |
MAPK8 | MAPK8 | E195; M200 | E195K; M200I | UCEC; SKCM |
CYP3A4 | CYP3A4 | F219 | F219L | UCEC |
Mutation: confirmed disease mutations among the predicted key allo-residues.
Cancer type: COAD: colon adenocarcinoma; SKCM: skin cutaneous melanoma; UCEC: uterine corpus endometrial carcinoma; GBM: glioblastoma multiforme; KIRC: kidney renal clear cell carcinoma; BLCA: bladder urothelial carcinoma.
Information of the allosteric proteins in the data set.
List of the Z-scores and ranking of allosteric pockets in the data set.
KeyAlloSite prediction results of Aurora A kinase.
List of the predicted key allo-residues in allosteric pockets.
Key allo-residues predicted by KeyAlloSite with different cutoffs.
KeyAlloSite prediction results of tyrosine-protein kinase ABL1.
The key allo-residues predicted by our method on Candida antarctica lipase B.
The confusion matrices of KeyAlloSite in different scenarios.
Comparison of KeyAlloSite and SCA methods.