Table 3.
Interactions formed by inhibitors with both chain B and C of BRAFV600E mutant protein dimer. Interactions similar to that of interactions formed by BGB283 are highlighted in bold.
| BRAFV600E mutant-Inhibitor Complex |
BRAFV600E mutant -BGB283 complex |
BRAFV600E mutant -VEM complex |
BRAFV600E mutant -CAPE complex |
BRAFV600E mutant -Wi-A complex |
BRAFV600E mutant -Wi-N complex |
BRAFV600E mutant -Ponatinib complex |
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|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Interactions | Chain B | Chain C | Chain B | Chain C | Chain B | Chain C | Chain B | Chain C | Chain B | Chain C | Chain B | Chain C |
| Hydrogen Bonds | Glu501 | Asn580 | Asp594 | GLN530 | Cys532 | His574 | Gln609 | Glu501 | Glu501 | |||
| Cys532 | Phe595 | Cys532 | Asp594 | His 574 | His574 | |||||||
| Asp594 | ||||||||||||
| Hydrophobic interactions | Ile463 | Phe468 | Ile463 | Ile463 | Ile463 | Ile463 | Ile463 | Val504 | Val504 | Ile463 | Ile463 | |
| Gly464 | Gly469 | Gly464 | Gly464 | Gly464 | Val504 | Leu505 | Leu505 | Val471 | Val471 | |||
| Gly466 | Val471 | Val471 | Trp531 | Gly466 | Leu505 | Ile513 | Ile513 | Ala481 | Ala481 | |||
| Val471 | Ala481 | Ala481 | Val471 | Val471 | Val471 | Leu567 | Leu514 | Leu514 | Val482 | Val482 | ||
| Ala481 | Leu514 | Val482 | Ala481 | Ala481 | Ala481 | Ile572 | Leu567 | Leu567 | Ala497 | Ala497 | ||
| Leu514 | Tyr538 | Leu505 | Leu505 | Leu514 | Leu514 | Ile573 | Ile572 | Ile572 | Val504 | Val504 | ||
| Trp531 | Phe583 | Leu514 | Ile513 | Trp531 | Cys532 | Tyr633 | Ile573 | Ile573 | Leu505 | Leu505 | ||
| Cys532 | Gly593 | Ile527 | Leu514 | Cys532 | Gly534 | Ile592 | Ile592 | Ile527 | Ile527 | |||
| Gly534 | Trp619 | Val528 | Leu515 | Phe583 | Val528 | Val528 | ||||||
| Phe583 | Cys532 | Leu516 | Phe583 | Gly593 | Ile572 | Ile572 | ||||||
| Phe583 | Ile527 | Phe595 | Phe595 | Ile573 | Ile573 | |||||||
| Gly593 | Trp531 | Phe597 | Ile592 | |||||||||
| Phe595 | Cys532 | |||||||||||
| Phe583 | ||||||||||||
| Gly593 | ||||||||||||
| Phe595 | ||||||||||||
| Polar and Charged Interactions | Ser465 | Ser467 | Ser465 | Gln461 | Ser467 | Glu501 | His574 | Thr529 | Lys483 | |||
| Lys483 | Lys483 | Lys483 | Arg462 | Lys483 | Lys483 | Lys507 | Asn500 | Thr508 | Gln496 | Gln530 | Asn500 | |
| Thr529 | Thr529 | Glu501 | Ser465 | Thr508 | Thr529 | Thr508 | Glu501 | His514 | Asn500 | Asp594 | Arg575 | |
| Glu533 | Lys578 | Thr529 | Lys473 | Gln530 | His574 | Thr508 | Arg575 | Glu501Thr508 | Glu501 | Asp576 | ||
| Ser535 | Asn580 | Asn580 | Thr529 | Ser535 | Arg575 | Arg575 | Asp594 | Asp594 | Asp576 | |||
| Ser536 | Asn581 | Asn581 | Gln530 | Ser536 | Asn581 | His608 | ||||||
| Asp594 | Asp594 | Asp594 | His539 | His608 | Asn580 | |||||||
| Ser616 | Asp594 | Asn580 | Gln612 | |||||||||
| Asp594 | ||||||||||||
| Pi-Pi Stacking | Phe468 | Phe595 | Phe595 | |||||||||