The constant pH simulations require a correction potential V MM (λ j ) for each titratable residue j. These correction potentials are the integrals of polynomial fits to the expectation value of ∂V /∂λ λ in reference state simulations at fixed λ values. 15 Thus, after integration, an n th order polynomial fit to ∂V /∂λ λ yields an (n + 1) th order polynomial function that represents V MM (λ). However, in the calculations of our implementation, the fit to ∂V /∂λ λ was used, rather than the V MM (λ). We thus refer to the fitting order as the order of the polynomial fit to the ∂V /∂λ λ .