Emilio,
A possible reason is that the net charges of the protein and of the
ligand have the same sign even if there is a salt bridge at the
binding site.
The changes in the electrostatic solvation energy and the Coulomb
energy upon binding in general have the opposite signs. This can be
understood by looking at the GB formula: there is a pairwise
(interaction) term that scales as q_i x q_j. This is similar to the
pairwise term in the Coulomb energy. This term would have the same
sign as the pairwise Coulomb term if it were without the pre-factor of
(1 - 1/80) since the pre-factor is always negative.
Hope this helps.
Ray
On Sat, Jan 5, 2013 at 11:44 AM, Emilio Angelina
<emilioluisangelina.hotmail.com> wrote:
>
> Dear all,
> I have performed MD simulations and MMPBSA analysis on a series of ligands in the binding site of a GPCR receptor. It seems strange to me that DeltaEEL be positive since in my case there is a salt bridge between the receptor and the ligand. It also seems strange for the same reasons that DeltaEGB be negative.
> The FINAL_RESULTS_MMPBSA.dat output is shown below.
> GENERALIZED BORN:
> WARNING: INCONSISTENCIES EXIST WITHIN INTERNAL POTENTIALTERMS. THE VALIDITY OF THESE RESULTS ARE HIGHLY QUESTIONABLEComplex:Energy Component Average Std. Dev. Std. Err. of Mean-------------------------------------------------------------------------------BOND 1283.9138 32.9110 3.2748ANGLE 3568.7667 51.8214 5.1564DIHED 4557.0217 26.1060 2.5976VDWAALS -3119.2732 21.5280 2.1421EEL -21488.9966 190.9942 19.00461-4 VDW 1573.5725 17.9417 1.78531-4 EEL 14660.8743 52.6229 5.2362EGB -9743.1158 179.9175 17.9025ESURF 180.1894 2.0514 0.2041
> G gas 1035.8792 194.0832 19.3120G solv -9562.9264 178.4552 17.7570
> TOTAL -8527.0472 63.3810 6.3066
>
> Receptor:Energy Component Average Std. Dev. Std. Err. of Mean-------------------------------------------------------------------------------BOND 1275.5349 32.8067 3.2644ANGLE 3552.1022 51.5383 5.1283DIHED 4548.2534 25.9616 2.5833VDWAALS -3080.9085 20.9271 2.0823EEL -21560.8980 199.0677 19.80801-4 VDW 1559.6602 17.9804 1.78911-4 EEL 14689.5611 52.5279 5.2267EGB -9648.9484 185.7658 18.4844ESURF 181.6462 2.0381 0.2028
> G gas 983.3052 201.4158 20.0416G solv -9467.3022 184.3024 18.3388
> TOTAL -8483.9969 63.9539 6.3637
>
> Ligand:Energy Component Average Std. Dev. Std. Err. of Mean-------------------------------------------------------------------------------BOND 8.3789 2.3596 0.2348ANGLE 16.6645 2.7870 0.2773DIHED 8.7705 2.0843 0.2074VDWAALS -3.7118 0.2799 0.0278EEL 34.3090 1.9865 0.19771-4 VDW 13.9123 1.2700 0.12641-4 EEL -28.6868 1.6891 0.1681EGB -61.4325 0.9973 0.0992ESURF 3.5740 0.0242 0.0024
> G gas 49.6366 5.1081 0.5083G solv -57.8585 0.9923 0.0987
> TOTAL -8.2219 4.5763 0.4554
>
> Differences (Complex - Receptor - Ligand):Energy Component Average Std. Dev. Std. Err. of Mean-------------------------------------------------------------------------------BOND 0.0000 0.0001 0.0000ANGLE 0.0000 0.0001 0.0000DIHED -0.0022 0.0065 0.0006VDWAALS -34.6528 2.7104 0.2697EEL 37.5924 15.8707 1.57921-4 VDW -0.0000 0.0001 0.00001-4 EEL 0.0000 0.0001 0.0000EGB -32.7349 10.7173 1.0664ESURF -5.0308 0.0796 0.0079
> DELTA G gas 2.9374 15.3958 1.5319DELTA G solv -37.7657 10.7322 1.0679
> DELTA TOTAL -34.8283 5.5203 0.5493
> Please suggest the source of error in this calculation. Thank you in advance
> Emilio Angelina Universidad Nacional del Nordeste Corrientes, Argentina
>
>
>
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Received on Sat Jan 05 2013 - 17:00:03 PST
