Table 2.
The binding energy values (kcal/mol) and the mode of interactions of compound 5b and the respective co-crystallized ligands with the active site of CDK4 and CDK6
| Protein | Compound 5b | |||
|---|---|---|---|---|
| Binding energy (Kcal/mol) | Interactions | Type of interaction | Bond distance (A0) | |
| CDK4 | − 26.7 |
O……ALA: 16 N…….LYS: 35 Cl…….SER: 52 Benzene…….TYR: 17 Benzene……..TYR: 17 Benzene…….PHE: 93 Benzene…….ALA: 33 Benzene…….VAL: 20 Benzene…….ALA: 157 Benzene……LEU: 147 Pyrazole……VAL: 20 Pyrazole……ALA: 157 |
Conventional hydrogen bond Conventional hydrogen bond Carbon hydrogen bond Pi-Pi T-shaped Pi-Pi T-shaped Pi-Pi T-shaped Pi-alkyl Pi-alkyl Pi-alkyl Pi-alkyl Pi-alkyl Pi-alkyl |
2.73 2.48 2.96 5.07 5.53 5.6 4.31 5.14 4.72 4.99 4.66 3.91 |
| CDK6 | − 30.77 |
O………VAL: 101 H………VAL: 101 Benzene…..ASP: 104 Benzene…..ASP: 104 Cl……….PHE: 98 Benzene…PHE: 98 |
Conventional hydrogen bond Carbon hydrogen bond Pi-anion Pi-anion Pi-alkyl Pi-Pi T-shaped |
2.47 2.53 4.04 4.97 3.66 5.66 |
| Co-crystallized ligand (Abemaciclib) | ||||
| CDK4 | − 36.3 |
Imidazole………..TYR: 17 Imidazole…………TYR: 17 N…………………….LYS: 35 F……………………..LYS: 35 NH………………….VAL: 96 N…………………….VAL:96 Pyrimidine……….VAL:96 H…………………….GLU:94 N……………………..HIS: 95 H……………………..ASP: 97 Benaene…………..PHE: 93 Benzene…………..PHE: 93 |
Pi-Pi Stacked Pi-alkyl Conventional hydrogen bond Conventional hydrogen bond Conventional hydrogen bond Conventional hydrogen bond Pi-alkyl Carbon hydrogen bond Carbon hydrogen bond Carbon hydrogen bond Pi-Pi T-shaped Pi-alkyl |
5.72 4.40 2.55 4.08 2.31 2.27 5.14 2.34 2.94 2.97 5.75 4.21 |
| Co-crystallized ligand (ribociclib) | ||||
| CDK6 | − 34.12 |
N…………………..VAL: 101 NH………………..VAL: 101 Pyrimidine………ILE: 19 Pyridine………….ILE: 19 H……………………ASP: 104 N…………………….ASP: 104 H……………………ASP: 104 O……………………ASP: 163 H……………………ASP: 163 Pyrazole…………..VAL: 77 Methyl…………….LYS: 43 H…………………….LYS: 43 |
Conventional hydrogen bond Conventional hydrogen bond Pi-alkyl Pi-alkyl Carbon hydrogen bond Attractive charge Carbon hydrogen bond Conventional hydrogen bond Carbon hydrogen bond Pi-alkyl Alkyl Alkyl |
2.35 1.96 5.26 4.72 2.53 4.00 2.70 2.02 2.64 4.96 4.14 4.50 |