Table 1.
RMSD values for top-scoring docking poses of crystallographic type-II ligands in DOLPHIN models of their respective kinase targets. Table entries are in the format Rmsd (Rank 1st correct, if not 1); NS = Not Sampled. Correct poses ranking first are colored green, within top three yellow, otherwise grey. All compound chemical structures can be found in Supp. Figure 1.
| ABL1 DFG-in | 406 | 7MP | GIN | KIN | PRC | STI |
|---|---|---|---|---|---|---|
| 2f4jA | 1.91 | 0.46 | 0.87 | 0.62 | 1.73 | 0.52 |
| 2g2iA | 1.14 | 0.65 | 1.11 | 0.67 | 1.67 | 0.76 |
| 2g2iB | 2.12(2) | 0.53 | 3.76(2) | 0.71 | 2.62(5) | 0.98 |
| 2gqgAa | 2.09(4) | 0.83 | 2.06(2) | 0.98 | 12.62(16) | 1.69 |
| 2gqgB | 1.85 | 1.90 | 0.85 | 0.89 | 2.06(8) | 1.75 |
| 2hz4A | 0.92 | 1.98 | 0.99 | 0.84 | 12.72(9) | 6.65(3) |
| 2hz4B | 1.37 | 1.03 | 0.85 | 0.62 | 1.92 | 1.55 |
| 2hz4C | 7.44(12) | 1.70 | 11.66(4) | 12.35(5) | 14.99 (40) | 11.11(26) |
| 2qohA | 0.88 | 0.68 | 0.89 | 0.73 | 1.56 | 0.60 |
| 2qohB | 1.09 | 0.97 | 1.23 | 0.64 | 1.58 | 0.81 |
| 2v7aAb | 4.32(44) | 8.22(10) | 10.34(61) | 0.97 | 9.97(47) | 13.19(51) |
| 2v7aBb | 13.19(149) | 9.36(23) | 10.49(NS) | 1.12 | 10.85(48) | 9.23(62) |
| 2z60Ab | 1.04 | 1.93 | 1.92 | 0.74 | 12.20(3) | 1.06 |
| BRAF1 DFG-in | BAX | LCK DFG-in | 1N8 | 242 | 9NH | STI | SRC DFG-in | STI |
|---|---|---|---|---|---|---|---|---|
| 2fb8A | 1.59 | 1qpcA | 1.13 | 0.77 | 1.01 | 1.49 | 1fmkAc | 11.91(NS) |
| 2fb8B | 0.62 | 1qpdA | 1.02 | 0.71 | 1.36 | 1.44 | 1y57A | 1.33 |
| 1qpeA | 1.28 | 1.63 | 1.30 | 1.61 | 1yi6A | 16.33(3) | ||
| 1qpjA | 1.03 | 0.47 | 0.83 | 1.39 | 1yi6Ba | 2.80(4) | ||
| 2of2A | 1.21 | 0.76 | 1.41 | 1.55 | 1yomBd | 5.18(57) | ||
| KIT DFG-in | STI | 2of4A | 1.23 | 0.74 | 1.05 | 1.50 | 2bdfAa | 7.11(2) |
| 1pkgAa | 4.11(3) | 2ofuA | 1.28 | 0.54 | 1.01 | 1.40 | 2bdfBa | 7.02(3) |
| 1pkgBa | 3.73(3) | 3lckA | 1.43 | 0.76 | 2.06(2) | 1.41 | 2bdjAa | 1.12 |
| 2hwoAd | 13.77(18) | |||||||
| 2oiqBa | 1.12 | |||||||
| MK14 DFG-in | 1PP | AQZ | B96 | BMU | L09 | L10 | L11 | LI2 | LI3 | WBT |
|---|---|---|---|---|---|---|---|---|---|---|
| 1m7qA | 0.62 | 3.16e(5) | 0.77 | 1.07 | 1.58 | 0.45 | 1.03 | 0.73 | 1.40 | 0.68 |
| 1oukA | 0.67 | 3.17e(4) | 0.80 | 0.93 | 1.40 | 0.68 | 0.77 | 0.79 | 1.50 | 0.75 |
| 1ouyA | 0.73 | 3.61e(15) | 0.76 | 1.12 | 1.81 | 0.49 | 1.19 | 0.99 | 1.50 | 0.90 |
| 1oz1A | 0.65 | 1.29 | 1.17 | 0.97 | 1.14 | 0.44 | 0.57 | 0.82 | 0.85 | 0.62 |
| 2okrA | 0.75 | 1.49 | 4.36(4) | 1.08 | 10.99(11) | 0.67 | 1.32 | 1.35 | 1.43 | 1.30 |
| 2okrD | 0.80 | 4.56e(NS) | 4.30(82) | 1.27 | 1.85 | 0.68 | 1.45 | 1.57 | 1.56 | 1.46 |
a
Narrow pocket
b
T315I imatinib-resistant mutation
c
Conserved salt bridge disrupted
d
Conserved salt bridge disordered
e
The part of the ligand occupying the hydrophobic “selectivity” pocket docked correctly with partial RMSD < 1A.