Hi,
I have performed MMGBSA calculations for a protein bound to a known drug molecule and the same protein bound to a designed inhibitor molecule. The EEL component for designed molecule showed positive value while that for the known drug molecule showed high negative value, although the final binding free energy (delta total) shows higher value for designed molecule. Does it mean that the newly desinged molecule has less interaction towards target protein.The results of the calculations are given below:
1)Known drug molecule
Differences (Complex - Receptor - Ligand):
Energy Component Average Std. Dev. Std. Err. of Mean
-------------------------------------------------------------------------------
BOND 0.0000 0.0001 0.0000
ANGLE 0.0000 0.0001 0.0000
DIHED -0.0031 0.0086 0.0003
VDWAALS -70.6426 3.2636 0.1300
EEL -209.8484 11.3086 0.4505
1-4 VDW 0.0000 0.0001 0.0000
1-4 EEL 0.0000 0.0001 0.0000
EGB 221.2930 10.7042 0.4265
ESURF -8.6492 0.2620 0.0104
DELTA G gas -280.4941 11.1058 0.4425
DELTA G solv 212.6437 10.7433 0.4280
DELTA TOTAL -67.8504 3.8190 0.1522
2) Designed drug molecule
Differences (Complex - Receptor - Ligand):
Energy Component Average Std. Dev. Std. Err. of Mean
-------------------------------------------------------------------------------
BOND 0.0000 0.0001 0.0000
ANGLE -0.0000 0.0001 0.0000
DIHED -0.0026 0.0088 0.0003
VDWAALS -78.0816 3.5686 0.1009
EEL 35.3564 36.6792 1.0374
1-4 VDW -0.0000 0.0000 0.0000
1-4 EEL 0.0000 0.0001 0.0000
EGB -15.5574 33.9529 0.9603
ESURF -9.6206 0.3180 0.0090
DELTA G gas -42.7277 36.2720 1.0259
DELTA G solv -25.1780 33.9229 0.9595
DELTA TOTAL -67.9057 4.1186 0.1165
--
Regards,
Sharon D'Morris
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Received on Mon Oct 30 2017 - 04:00:02 PDT
