Re: [AMBER] MMPBSA Delta total results

From: Ray Luo <rluo.uci.edu>
Date: Fri, 7 Jul 2017 12:17:25 -0700

Hi All,

Regarding the choices of nonpolar, as Dave pointed out, inp=2 is the
newer approach and is still under development. The inp=1 was set to
default in the later releases via patching in Amber 16. Somehow, this
might not go into the Amber17 release automatically. I'm looking into
this.

So far inp=2 tends to give a delta G too positive for large ligands,
i.e. proteins or nucleic acids as it was optimized for small molecules
and point mutations. In contrast inp=1 tends to give a delta G too
negative as it does not consider the volume effect in the van der
Waals interactions.

The overall effect is that inp=2 leads to smaller absolute delta G and
inp=1 leads to larger absolute delta G. This may result in slightly
smaller correlation coefficients with respect to experimental values
in inp=2 results because its range of data is smaller.

However, you should also look at RMSD's of relative delta G's with
respect to experiment due to the approximate nature of MMPBSA. This is
the place you may see much better improvement in the use of inp=2. In
the end, your computation is meant to guide/predict delta G changes
upon such mutational changes or different ligands.

All the best,
Ray

--
Ray Luo, Ph.D.
Professor of Structural Biology/Biochemistry/Biophysics,
Chemical Physics, Biomedical Engineering, and Chemical Engineering
Department of Molecular Biology and Biochemistry
University of California, Irvine, CA 92697-3900
On Fri, Jul 7, 2017 at 6:32 AM, David Case <david.case.rutgers.edu> wrote:
> On Fri, Jul 07, 2017, Elvis  Martis wrote:
>
>> inp=2 is default.
>
> My personal advice, based mainly on looking at other people's results:
>
> inp=1 is a more stable option, and "works" for a wider range of inputs (e.g.
> nucleic acids, odd ligands, odd geometries).  I would recommend using this
> option first, especially when you are trying to see if things make sense.
>
> inp=2 can work well in cases close to what it was designed for.  But note
> that the absolute energies for inp=2 may be quite different from those for
> inp=1, even when trends in binding affinities are the same as (or better than)
> those from inp=1.
>
> Ray can weigh in here with more detailed advice.  My conclusions should be
> taken with caution, since I don't do very many of these calculations any more.
> And I don't know what the defaults are--may depend on how you invoking the
> pbsa codes.
>
> ....dac
>
> [Shameless plug: MM/RISM avoids the issue of dividing the solvation free
> energy into to polar and non-polar terms.  But it hasn't been used nearly as
> widely, and one has to be careful to use "corrected" estimates of the
> solvation free energy.]
>
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Received on Fri Jul 07 2017 - 12:30:02 PDT