> 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 - 10:30:02 PST
