Molecular Dynamic Simulation to Explore the Molecular Basis of Btk-PH Domain Interaction with Ins(1,3,4,5)P4
Table 1
Ranked calculated binding free energies (kcal/mol) using MM/PBSA for the twelve protein-ligand systems.
ELE
VDW
PB
SA
PBTOT
WT
−3031.77 (9.01a)
−0.16 (0.07)
2961.60 (7.63)
−4.28 (0.47)
−74.61 (5.10)
−45.29 (1.43)
−29.32 (1.49)
K12R-R28C
−3119.66 (10.33)
−0.12 (0.05)
3044.04 (8.61)
−4.25 (0.18)
−79.99 (3.37)
−52.50 (1.45)
−27.49 (1.06)
K19E
−3143.08 (8.92)
−0.17 (0.03)
3069.08 (7.38)
−4.21 (0.16)
−78.38 (5.33)
−51.09 (1.60)
−27.29 (0.73)
K12R-R28H
−3029.46 (8.74)
−0.05 (0.02)
2962.73 (6.43)
−4.12 (0.21)
−73.30 (2.02)
−51.66 (1.37)
−21.64 (0.66)
E41K
−2855.47 (7.73)
−0.28 (0.16)
2789.39 (5.95)
−4.16 (0.23)
−70.52 (3.12)
−50.08 (1.52)
−20.44 (0.38)
K12R
−2922.34 (9.17)
−0.08 (0.03)
2859.80 (8.38)
−4.30 (0.21)
−66.92 (3.62)
−52.84 (1.57)
−14.08 (0.94)
R28C
−2612.17 (5.95)
−1.90 (0.23)
2552.82 (5.03)
−3.69 (0.16)
−64.94 (1.87)
−57.28 (2.47)
−7.66 (0.03)
R28H
−2591.08 (6.16)
−1.61 (0.17)
2533.38 (4.65)
−3.70 (0.17)
−63.01 (1.16)
−56.80 (2.54)
−6.21 (0.02)
S14F
−2573.79 (7.06)
−3.37 (0.74)
2545.38 (6.99)
−3.42 (0.25)
−35.20 (2.47)
−57.49 (3.02)
22.29 (0.98)
L11P
−2599.24 (7.61)
−1.75 (0.41)
2578.10 (6.70)
−3.94 (0.33)
−26.83 (1.42)
−58.75 (4.47)
31.92 (2.02)
Y40N
−2550.35 (7.0)
−2.57 (0.59)
2531.48 (6.23)
−3.92 (0.27)
−25.36 (1.84)
−58.34 (3.89)
32.98 (1.68)
F25S
−2501.74 (7.17)
−2.59 (0.69)
2487.39 (6.64)
−3.77 (0.19)
−20.71 (1.54)
−58.32 (4.15)
37.61 (1.82)
The statistical error was estimated on the basis of the deviation between block averages. ELE: electrostatic energy; VDW: van der Waals energy; PB: the PB solvation energy; SA: the surface area energy (nonpolar solvation energy); PBTOT: sum of ELE, VDW, PB, and SA. The absolute temperature () was set to 300 K in the MM-PBSA calculations. : subtracting from PBTOT.