Table 1.
Structural properties of BRAFWT-Inhibitor dimer complexes and BRAFV600E mutant-Inhibitor dimer complexes.
| Parameters |
MM-GBSA Binding energy (Kcal/mol) |
DFG motif Conformation |
αC-helix orientation |
Binding Energy of two BRAF-MEK1 monomer |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Protein-Inhibitor Complex | BRAFWT | BRAFV600E | BRAFWT | BRAFV600E | BRAFWT | BRAFV600E | BRAFWT-MEK1 dimer | ||||||
| Chain | B | C | B | C | B | C | B | C | B | C | B | C | A-B:C-D |
| ATP | In | In | Out | Out | In | In | Out | Out | |||||
| BGB283 | −49.71 | −72.14 | −103.85 | --93.35 | In | In | Out | Out | In | In | Out | In | −10.9 |
| VEM | −62.28 | −73.20 | −84.69 | −84.07 | In | In | Out | Out | In | In | Out | In | −9.6 |
| Ponatinib | −66.87 | −78.33 | −96.21 | −106.27 | In | In | Out | Out | Out | Out | Out | In | – |
| CAPE | −51.42 | −57.36 | −60.35 | −60.37 | In | In | Out | Out | In | In | Out | Out | −11.0 |
| Wi-A | −40.23 | −43.29 | −39.91 | −53.37 | In | In | Out | Out | In | In | Out | In | −10.7 |
| Wi-N | −50.14 | −33.43 | −33.36 | −54.72 | In | In | Out | Out | In | In | Out | In | −9.3 |