Table 1.
Calculation of LGFEs of JY-1-106
| Total LGFEs | Minimized | Langevin dynamics | Explict solvent MD | ||||
|---|---|---|---|---|---|---|---|
| Bcl-xL |
|
|
|
|
|||
| |
F |
-10.2 (4.3) |
-10.6 (4.2) |
-13.8 (4.1) |
|||
| |
B |
-10.1 (3.9) |
-10.6 (4.0) |
-15.8 (2.7) |
|||
| Mcl-1 |
|
|
|
|
|
||
| |
F |
-7.3 (2.9) |
-7.2 (2.3) |
-8.7 (1.5) |
|||
| |
B |
-7.8 (3.9) |
-7.0 (2.2) |
-7.5 (2.2) |
|||
| Difference, Mcl-1 - Bcl-xL | |||||||
| |
F |
2.9 |
3.4 |
5.1 |
|||
| |
B |
2.3 |
3.6 |
8.3 |
|||
| Group contributions |
Minimized |
Langevin dynamics |
Explict Solvent MD |
||||
| |
|
Aromatic |
Aliphatic |
Aromatic |
Aliphatic |
Aromatic |
Aliphatic |
| Bcl-xL |
|
|
|
|
|
|
|
| |
F |
-6.8 |
-3.4 |
-5.9 |
-4.4 |
-11.3 |
-2.5 |
| |
B |
-7.1 |
-3.0 |
-7.2 |
-3.3 |
-12.4 |
-3.5 |
| Mcl-1 |
|
|
|
|
|
|
|
| |
F |
-4.7 |
-2.5 |
-4.9 |
-2.2 |
-4.0 |
-4.7 |
| |
B |
-4.6 |
-3.1 |
-5.5 |
-1.5 |
-5.3 |
-2.2 |
| Difference, Mcl-1 - Bcl-xL | |||||||
| |
F |
2.1 |
0.9 |
1.0 |
2.2 |
7.3 |
-2.2 |
| B | 2.5 | -0.1 | 1.7 | 1.8 | 7.1 | 1.3 | |
Total Ligand Grid Free Energies (LGFE, kcal/mol) for JY-1-106 binding to Bcl-xL and Mcl-1 based on the minimization, Langevin Dynamics and Explicit Solvent MD simulation approaches along with LGFE group contributions summed over the aromatic and aliphatic functional groups for Bcl-xL and Mcl-1.
Results are presented for both forward (F) and backward (B) orientations of JY-1-106 and differences (Mcl-1 – Bcl-xL) are presented for all values. Values in paranthesis for the total LGFEs are standard errors.