> On Jul 2, 2014, at 3:08 AM, Zeinab Tavasoli <zeinabtavasoli.gmail.com> wrote:
>
> Dear Users'
>
> I am performing free energy calculation with MM-PBSA.py for a crystal
> structure of a protein-ligand complex.I have used MM-PBSA module after
> running 10 ns md simulation.
> Since I don't need gb namelist, I have used this input file:
>
>
>
>
>
>
>
> *Input file for running PB and GB in serial&general startframe=1,
> endframe=25000, keep_files=2,/&pb istrng=0.100, /*
>
> Although I have checked the structure of the complex after production and I
> am sure about the binding of ligand to its proper site, ΔG value is
> positive. Here is the end part of the FINAL_RESULT.dat file:
>
>
>
>
> *Differences (Complex - Receptor - Ligand):Energy Component
> Average Std. Dev. Std. Err. of
> Mean-------------------------------------------------------------------------------*
> *BOND 0.0000 0.0001
> 0.0000*
> *ANGLE 0.0000 0.0000
> 0.0000*
> *DIHED 0.1101 0.1072
> 0.0024*
> *VDWAALS -51.3535 4.0635
> 0.0908*
> *EEL 106.0784 20.1745
> 0.4510*
> *1-4 VDW 0.0000 0.0001
> 0.0000*
> *1-4 EEL -0.0000 0.0001
> 0.0000*
> *EPB -77.7007 17.4595
> 0.3903*
> *ENPOLAR -42.1622 2.6622
> 0.0595*
> *EDISPER 69.0762 4.0390
> 0.0903*
>
> *DELTA G gas 54.8350 20.3812
> 0.4556*
> *DELTA G solv -50.7868 17.6481
> 0.3945*
>
> *DELTA TOTAL 4.0482 6.0860
> 0.1361*
>
>
> I don't know where to look for the origin of this problem
Another thing to look at is the nonpolar solvation free energy method you are using. The default value for PB calculations tends to give much higher binding free energies than the typical approach where the nonpolar energy is represented as a simple proportionality of the SASA.
As the nonpolar contribution to binding is +27 kcal/mol (and typical contributions from the simple SASA model is more like 5 kcal/mol), this will certainly make your binding free energy negative. However, that doesn't necessarily mean that the absolute binding free energy is more reliable. MM PBSA calculations are more appropriate for relative binding free energies.
HTH,
Jason
--
Jason M. Swails
BioMaPS,
Rutgers University
Postdoctoral Researcher
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Received on Wed Jul 02 2014 - 07:30:04 PDT
