Well, I do not expect quantitative results from these calculations. I am
doing these calculations to distinguish between multiple binding sites (for
same ligand) in a system. Experimentally there not any evidence of
difference in binding energies for those sites but from Mm/PBSA I had found
two groups of binding site with diff binding energies. Now when I set salt
concentration there binding strength is reverse (weak binding site becomes
strong and vice-versa). This is where I got doubtful about the results
because including salt changes the qualitative meaning of results.
/Mish
On Thu, Mar 8, 2012 at 7:00 PM, Thomas Cheatham III <tec3.utah.edu> wrote:
>
> > I have question related to salt the salt concentration and ionic strength
> > values used in MM/GBSA and MM/PBSA calculations, respectively. Initially
> I
> > was using perl script and I did not care much about these two values ( so
> > they were set to zero). Now when I switched to new python script, I
> noticed
> > in the manual that value of saltconc was set to 0.15 (for IGB=5) and 0.10
> > (for igb=2) in sample input file. Also istrng=0.15 is mentioned for PB
> > calculations.
> >
> > I want to know, if this should effect the binding energies too much ? and
> > also the reason to have those values (when default is 0.0) there in
> sample
> > input files of manual ? I looked for experimental detail in my case and
> > what I can see is ITC measurement were done in 100mM Tris buffer at pH
> 7.5
> > . Can you please suggest me optimal (theoretically) values of saltconc
> and
> > istring to compare these experimental values taken in 100mM Tris buffer
> at
> > pH 7.5 ?
>
> These are rather quick calculations, so why not check yourself? My
> expectation is that these changes will not have a drastic effect on the
> calculated values. Also, it makes sense that the sample inputs
> (which represent actual sample inputs people actually ran with) include
> salt since we do not live in a no-salt environment.
>
> Often MM-PBSA is treated as a black box when in fact the results will
> depend on choices made so it is a good idea to experiment and understand
> the implications of your particular choices, particularly if the results
> seem unreasonable. The black-box nature of MM-PBSA can hide errors.
>
> As normal binding constants are in the micromolar to nanomolar range,
> based on dG = -RT ln K you expect binding free energies in the -8 to -12
> kcal/mol range. It's more complicated due to rotational/translational
> entropy losses upon binding, loss of vibrational freedom, etc and other
> factors (which may not be included, or included correctly in the MM-PBSA
> approach). However, if you calculate a binding constant of -100 kcal/mol,
> something is wrong... See papers and reviews by Gilson on the gory
> details of dG binding.
>
> --tec3
>
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Received on Thu Mar 08 2012 - 11:30:03 PST
