Table 3 Docking information for the interaction of designed compounds with V600E-BRAF (PDB ID: 3OG7)
Molecular System | Free binding energy (kcal mol−1) | Category | From | To | Types | Distance |
|---|---|---|---|---|---|---|
BRAF/39 | − 7.0 | Hbond Hbond Hbond Hbond Electrostatic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic | Comp 39 Comp 39 Comp 39 LYS483 LYS483 Comp 39 Comp 39 Comp 39 Comp 39 Comp 39 Comp 39 Comp 39 TYR538 PHE583 PHE583 | GLY534 ILE463 SER465 Comp 39 Comp 39 PHE583 ILE463 VAL471 ALA481 CYS532 LYS483 LEU514 Comp 39 Comp 39 Comp 39 | Carbon Hbond Carbon Hbond Carbon Hbond Carbon Hbond Pi-Cation Pi-Pi Stacked Alkyl Alkyl Pi-Alkyl Pi-Alkyl Pi-Alkyl Pi-Alkyl Pi-Alkyl Pi-Alkyl Pi-Alkyl | 3.48655 3.56658 3.42361 3.56901 3.9777 4.29154 4.9305 4.42429 4.44566 4.74288 4.91316 5.30238 5.01065 4.98907 4.70529 |
BRAF/N1 | − 11.7 | Hbond Hbond Hbond Hbond Halogen Other Other Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic | LYS578 N1 N1 N1 CYS532 N1 CYS532 N1 N1 N1 N1 N1 N1 N1 N1 PHE468 TRP531 TYR538 TYR538 PHE583 TRP619 TRP619 | N1 N1 ASN581 ASP594 N1 PHE583 N1 PHE583 LEU618 LEU618 LEU654 LEU618 VAL471 CYS532 VAL471 N1 N1 N1 N1 N1 N1 N1 | Conventional Hbond Carbon Hbond Carbon Hbond Carbon Hbond Halogen (Cl, Br, I) Pi-Sulfur Pi-Sulfur Pi-Pi Stacked Alkyl Alkyl Alkyl Alkyl Alkyl Alkyl Pi-Alkyl Pi-Alkyl Pi-Alkyl Pi-Alkyl Pi-Alkyl Pi-Alkyl Pi-Alkyl Pi-Alkyl | 2.17195 3.56998 3.62103 3.76296 3.36466 4.92104 5.40241 3.83358 4.40618 4.85919 4.48542 4.49995 4.49079 4.338 5.31215 4.96372 4.65719 4.38479 4.97273 4.84398 4.96805 4.76483 |
BRAF/N2 | − 12.8 | Hbond Hbond Hbond Hbond Hbond Hbond Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic | N2 SER536:HN N2 N2 N2 SER536:CB N2 N2 N2 N2 N2 N2 N2 N2 N2 N2 TYR538 TYR538 PHE583 TRP619 | CYS532 N2 N2 GLY615 N2 N2 TYR538 TRP531 PHE583 TRP531 LEU618 LEU654 VAL471 ALA481 CYS532 ILE463 N2 N2 N2 N2 | Conventional Hbond Conventional Hbond Carbon Hbond Carbon Hbond Carbon Hbond Carbon Hbond Pi-Sigma Pi-Pi Stacked Pi-Pi Stacked Pi-Pi Stacked Alkyl Alkyl Alkyl Pi-Alkyl Pi-Alkyl Pi-Alkyl Pi-Alkyl Pi-Alkyl Pi-Alkyl Pi-Alkyl | 2.53681 2.96436 3.46536 3.447 3.79629 3.45633 3.56439 5.58757 4.2708 4.8213 4.98968 4.74922 3.8191 4.4391 4.76504 4.99883 4.69283 4.74658 4.56957 4.81074 |
BRAF/N3 | − 12.7 | Hbond Hbond Hbond Hbond Hbond Other Other Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic | CYS532 LYS578 N3 N3 N3 N3 CYS532 N3 N3 N3 N3 N3 N3 N3 N3 N3 TYR538 TRP619 TRP619 | N3 N3 SER465 ASN581 ASP594 PHE583 N3 PHE583 LYS578 ILE617 LEU618 ILE617 ARG662 VAL471 VAL471 LEU514 N3 N3 N3 | Conventional Hbond Conventional Hbond Carbon Hbond Carbon Hbond Carbon Hbond Pi-Sulfur Pi-Sulfur Pi-Pi Stacked Alkyl Alkyl Alkyl Alkyl Alkyl Alkyl Pi-Alkyl Pi-Alkyl Pi-Alkyl Pi-Alkyl Pi-Alkyl | 2.41199 2.38112 3.6557 3.53249 3.47966 5.37771 5.43102 3.88023 4.89364 5.10057 3.97565 4.57335 4.16846 4.37577 5.27903 5.49117 4.78575 4.86122 4.80602 |
BRAF/N4 | − 12.9 | Hbond Hbond Hbond Hbond Hydrophobic Other Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic | SER536 SER536 N4 N4 N4 CYS532 N4 N4 N4 N4 N4 TYR538 TYR538 TYR538 TRP619 TRP619 | N4 N4 N4 N4 TYR538 N4 TRP531 PHE583 LEU618 LEU654 ILE463 N4 N4 N4 N4 N4 | Conventional Hbond Conventional Hbond Carbon Hbond Carbon Hbond Pi-Sigma Pi-Sulfur Pi-Pi Stacked Pi-Pi Stacked Alkyl Alkyl Pi-Alkyl Pi-Alkyl Pi-Alkyl Pi-Alkyl Pi-Alkyl Pi-Alkyl | 2.8161 2.96186 3.58087 3.71491 3.56324 4.93206 5.60961 3.89772 5.22936 4.8599 4.78846 5.21844 4.99332 4.4122 4.76496 5.23231 |
BRAF/Vem | − 11.3 | Hbond Hbond Hbond Hbond Electrostatic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic Hydrophobic | Vem Vem PHE595 GLY596 LYS483 Vem Vem Vem Vem Vem Vem Vem Vem Vem TRP531 PHE583 PHE595 | CYS532 GLN530 Vem Vem Vem TRP531 PHE583 LEU505 Vem ALA481 LEU514 CYS532 LYS483 ILE463 Vem Vem Vem | Conventional Hbond Conventional Hbond Conventional Hbond Conventional Hbond Pi-Cation Pi-Pi Stacked Pi-Pi Stacked Alkyl Alkyl Pi-Alkyl Pi-Alkyl Pi-Alkyl Pi-Alkyl Pi-Alkyl Pi-Alkyl Pi-Alkyl Pi-Alkyl | 3.0153 2.35105 2.66721 2.06321 4.24755 5.79107 4.70902 3.98089 5.29789 3.84027 5.10949 4.96308 4.39203 4.64053 4.72282 4.8485 4.65347 |