You have to do some things by yourself. This is largely a matter of experimentation: adjust your charges a bit, see how the water interactions are affected, adjust them again, repeat ad nauseum
... As the CHARMM run takes mere seconds, you can do several of these cycles per minute if you organize yourself a bit.
Deviation of 2 kcal/mol are not
acceptable as such. In general, we aim to get all the interaction energies within 0.2 kcal/mol
, as mentioned in the CGenFF paper and demonstrated in the tutorial. But there are a few exceptions. If you have two water interactions for the same HB acceptor
, then in some cases
it is impossible to get them all right, because any adjustment of the charges will affect both of them in the same direction. If that's the case
, then one should either
go for the strongest interaction, or
make a compromise between the two interactions. To decide whether to make a compromise or go for the strongest, you look at the difference between the two QM interaction energies
, and see if it's lower or higer than 2 kcal/mol; see my previous post. But there are cases in which you can get both of them right - I'd recommend you play with the balance of charge between the 3 carbons and see what the effect is.
iii) keep the same charge on the methyl hydrogens?
Yes, they should be kept at 0.09. And the two carboxylate oxygens should always be given the same charge because they're chemically equivalent. And the total charge of the molecule should be kept at -1 at all time. This can be most easily accomplished by shifting charge around. For instance, you could try to subtract 0.02 charge units from each of the carboxylate oxygens (making them more negative) and move the resulting 2x0.02=0.04 charge units onto the carboxylate carbon (making it more positive).
As this leaves you only 4 degrees of freedom, this is a really easy assignment to begin with.
The initial guess water interactions look not too bad to begin with; in fact, the ones on O2 and O12 look pretty good. But do play around with the charges a bit, you might get them better. Keep an eye on the dipole moments while doing so; we want to overestimate them a bit (although they're less important than the interaction energies, especially for charged systems). And try to keep the charges physical; it's sometimes tempting to run off in an unphysical direction. If you're not sure about what's physical, try to not deviate more than 0.1 or 0.2 charge units from your Merz-Kollman initial guess.