Re: [AMBER] Disparities between dG solv from GB and PB Models

From: Ray Luo <rluo.uci.edu>
Date: Sat, 13 Feb 2021 14:21:27 -0800

Mish,

If you want to compare MMPBSA and MMGBSA, you'll have to use radiopt=0
and inp=1.

You are using inp=2, which is a new approach to compute the nonpolar
solvation free energies. It can't be compared with inp=1 or the SA
part in GBSA directly. Instead, you may want to compare computed delta
delta G from all approaches with experimental values to see which
approaches give you lower RMSD's.

All the best,
Ray

All the best,
Ray

--
Ray Luo, Ph.D.
Professor of Structural Biology/Biochemistry/Biophysics,
Chemical and Materials Physics, Chemical and Biomolecular Engineering,
Biomedical Engineering, and Materials Science and Engineering
Department of Molecular Biology and Biochemistry
University of California, Irvine, CA 92697-3900
On Sat, Feb 13, 2021 at 1:56 PM mish <smncbr.gmail.com> wrote:
>
> Dear all,
>
> I am trying to calculate the binding free-energy of hydrophobic molecules
> with a protein using MM/GBSA, and MM/PBSA approaches. I did enthalpy
> calculations using igb 1, 2, 5, 7, and 8 separately with appropriate VDW
> radii sets mentioned in the Amber20 manual. This all looked fine (obtained
> binding energies in the range of -50 to -70 kcal/mol) until I did MM/PBSA
> calculations on the same system. While doing MM/PBSA, I get +ve binding
> free energy, and a difference of about +70 kcal/mol is caused by large
> positive dE_SA (ENPLOAR + EDISPER) values in MM/PBSA (~ +40 kcal/mol). I
> used radiopt=0, cavity_surften-0.378, cavity_offset=-0.5692 with all four
> vdW radii sets (bondi, mbondi, mbondi2, mbondi3)  and I am getting exactly
> same dE_SA values.
>
> I wonder what could be the source of such a different discrepancy between
> MM/GBSA and MM/PBSA entropy values. I am worried that something might be
> technically wrong as the MD simulations were run using CHARMM forcefield,
> and I am convertingCHARMM topology file into Amber topology using parmed. I
> believe it is still using CHARMM forcefield parameters in the calculations
> (other than vdW radii sets that I changed using --radii option in the
> ante-MMPBSA.py script. Can someone help understand why dE_SA (ENPLOAR +
> EDISPER) is positive and different from dE_SA (ESURF) from MM/GBSA?
>
> Thanks,
> Mish
> _______________________________________________
> AMBER mailing list
> AMBER.ambermd.org
> http://lists.ambermd.org/mailman/listinfo/amber
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber

Received on Sat Feb 13 2021 - 14:30:02 PST