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

From: <psu4.uic.edu>
Date: Tue, 24 Mar 2015 12:06:49 -0500

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
latest bug fix 26.















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Received on Tue Mar 24 2015 - 10:30:02 PDT
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