Re: [AMBER] Best suitable 'igb' value for MMPBSA.py calculation

From: Ray Luo, Ph.D. <ray.luo.uci.edu>
Date: Fri, 23 Oct 2015 11:23:29 -0700

Just my 2c since we are also looking at this. In general, this is case
dependent. So you'll have to investigate your own system by trying
different models.

Another issue is don't just look at R or R^2, also look at RMSD of
relative binding free energies. Correlation coefficients strongly
depend on the range of data used. Since absolute binding free energies
by MMPBSA are usually very large, these correlation measures look good
"on paper", but the RMSD of relative free energies may not be great
for a given model.

Similar statement can be said about the entropy term. Often times, the
correlation measures are reduced when the entropy term is added since
the absolute numeric ranges are reduced, but RMSD may improve. If you
look at correlations only, you'd think use of the entropy term is bad
for MMPBSA calculations.

All the best,
Ray

--
Ray Luo, Ph.D.
Professor
Biochemistry, Molecular Biophysics, Chemical Physics,
Chemical and Biomedical Engineering
University of California, Irvine, CA 92697-3900
On Fri, Oct 23, 2015 at 8:20 AM, Hai Nguyen <nhai.qn.gmail.com> wrote:
> I don't have an answer for you since I have never done mmgbsa. But you
> might want to check Pin-Chih Su et al's paper (below). They compared all GB
> models in Amber.
>
> Su, P.-C.; Tsai, C.-C.; Mehboob, S.; Hevener, K. E.; Johnson, M. E.,
> Comparison of radii sets, entropy, QM methods, and sampling on MM-PBSA,
> MM-GBSA, and QM/MM-GBSA ligand binding energies of F. tularensis enoyl-ACP
> reductase (FabI). Journal of Computational Chemistry 2015, 36 (25),
> 1859-1873.
>
> http://onlinelibrary.wiley.com/doi/10.1002/jcc.24011/abstract
>
> Hai
>
> On Fri, Oct 23, 2015 at 10:02 AM, anu chandra <anu80125.gmail.com> wrote:
>
>> Dear Amber users,
>>
>> I am working with a protein-ligand system, where the protein comprise of
>> two domains, say A and B and the ligand bind to domain A. I am trying to
>> calculate the free energy of ligand binding in presence and absence of
>> domain B ( I have carried two different simulations, with and without
>> domain B).
>>
>>       With igb=2, I got binding free energy of 85.6  without domain B and
>> 91.7 with domain B, and difference is ~6 kcal/mol.  With igb=5, the binding
>> free energy is 110.5  without domain B and 121.6 with domain B, and
>> difference is ~11 kcal/mol. Which values are more reliable, with igb=2 or
>> with igb=5? Will it be possible to consider the difference of 6 or 11 (
>> either of it depends to the chosen igb value) as a measurement of influence
>> of domain B on ligand binding?
>>
>>
>> Many thanks
>> Anu
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Received on Fri Oct 23 2015 - 11:30:03 PDT