Re: [AMBER] EGB and ESCF might not be converged if the net charge not equal to 0 in the QM/MM-GBSA

From: Gerald Monard <>
Date: Fri, 27 Mar 2015 09:27:39 +0100


What you see is something very general for QM/MM calculations, although
I'm not aware of any papers discussing it: you should avoid a
non-neutral QM region, especially in the case of a charged MM region.
It comes from the QM/MM electrostatic interactions. The point charges of
the MM part polarizes the QM part. You can think of your MM point charge
set in terms of a multipolar development at the center of the MM region
(total charge + dipole + quadrupole + etc.). You can do the same for the
QM region. If the MM and the QM regions are charged, the main component
of the electrostatic QM/MM interaction is a charge-charge interaction
whose value is the total charge of the QM region times the total charge
of the MM region divided by the distance between the two centers. If you
are "lucky", these two centers are close and the electrostatic
interactions is very large.

In your case, when you use a trajectory, these centers move along the
trajectory. This will yield large changes if the two centers are close.

If your MM part and the QM part are neutral, then the main interaction
component is a dipole-dipole interaction that is less susceptible to the

If you want to verify my saying, check the total charge of the MM part,
and make it neutral if it is not.
You can also turn the MM charges off and check the differences in ESCF.
I would guess that the numbers will change a lot in the case the QM part
is charged.

My two cents,


On 03/24/2015 06:06 PM, wrote:
> Dear Amber,
> We have used a series of protein-ligand binding trajectories to test
> MM/PBSA, MM/GBSA and QM-MM/GBSA extensively. However, if we include NADH,
> which has net charges equal to -2, into the QM region, EGB and ESCF (QM d
> Gelectro) don’t converge in some of the test cases (ESCF in dGbind can
> fluctuate really widely: -700~100 kcal/mol for example ). Therefore the
> abnormal behavior makes large and positive dGbind (for example, dGbind =
> 34.37 kcal/mol. For example, the dGbind calculated from MM/GBSA using the
> same trajectories here, is -30 kcal/mol). This happens in igb=1,2,5,7,8 and
> various effective radii settings.
> However, if the net charge is equal to 0 in the QM-MM region (NADH not
> included), QM-MM/GBSA can offer converged and high agreements with
> experimental data as MM/PBSA and MM/GBSA do, across various igb and effective
> radii setting. Could any guru enlighten? The following is an example of
> QM-MM/GBSA input, which includes the NADH cofactor (residue 101) and the
> ligand (residue 100). Therefore, the net charges of QM regions in both
> complex and receptor are -2 since the ligand doesn't have any charge.
> The test is performed in AmberTools13/ the latest bug fix 26 and
> Amber12/the
> latest bug fix 26.
> &general
> keep_files=2,interval=10,
> /
> &gb
> igb=8,
> saltcon=0.100,
> ifqnt=1,
> qmcharge_lig=0,
> qmcharge_com=-2,
> qmcharge_rec=-2,
> qm_residues=100,101,
> qm_theory='PM3',
> /
> Best,
> Henry
> _______________________________________________
> AMBER mailing list

  Prof. Gerald MONARD
  SRSMC, Université de Lorraine, CNRS
  Boulevard des Aiguillettes B.P. 70239
  F-54506 Vandoeuvre-les-Nancy, FRANCE
  e-mail :
  tel.   : +33 (0)383.684.381
  fax    : +33 (0)383.684.371
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Received on Fri Mar 27 2015 - 01:30:02 PDT
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