Does ASH ensure total charge convervation during QM/MM simulation? about ash

[RagnarB83]

So ASH currently only does electrostatic embedding (mechanical embedding is actually not fully enabled yet) and the MM charges of the QM-region are then set to zero during the calculation of the MM-energy (by OpenMM) to avoid double-counting. Any defined pointcharges of the QM-atoms are thus never actually used.

During QM/MM, if the QM-region has a zero total charge:

• no problem, the QM-atom charges are set to zero and the total MM charge does not change.

During QM/MM, if the QM-region has non-zero total charge (e.g. -1 or +1) then you are right that this would cause a problem, since if the MM-charges of the QM-atoms have been set to zero (in order to avoid QM-MM electrostatic double-counting) then the total MM-system charge no longer sums to zero, which could cause an issue for the MM-part PME electrostatics (only if periodic electrostatics are turned on). OpenMM does deal with this automatically (outside ASH) by adding a uniform neutralizing charge distribution for non-zero charged systems. From an energetic point of view, this scenario would give a systematic shift in total MM energy and total QM/MM energy. However, the MM-energy is not that well-defined anyway and this systematic shift should have no effect when we calculate relative energies for systems with QM-regions set up in the same way (same charge). For an ionization energy (where the QM-region charge changes), one might have an issue and perhaps the MM-energy difference is not very physical then.

For the QM-part (with embedded pointcharges included and calculated by the QM-code), it would depend on how we do the calculation. Most QM-codes interfaced to ASH actually have no periodicity so the problem does not come up there (CP2K is the first one so far). On the other hand, the QM/MM energy expression is not consistent if the MM-part is periodic and the QM-part is not.
Proper periodic QM/MM MD simulations in ASH is not really possible yet.
I will take a look at the Amber paper.