Thanks for your reply. Yes, free energy methods seem to be more nuanced - but here, I'm not sure that I should mess with the QCOR parameter as I have a solvated, periodic system. In thinking about it more, it isn't clear to me that neutralization with counterions (hence allowing the use of PME) would necessarily impact the micro-environment of the protein where the charge change is taking place? I'm trying to avoid constant pH simulations....

Last edited by ca4930; 07/20/21 05:46 PM.