Table 1.

Overview of the simulated systems and simulation conditions. For the different systems (Sec. 4A), explicit-solvent MD simulations were carried out at 300 K and constant volume (effective solvent density appropriate for water at 1 bar) using cubic periodic computational boxes and lattice-sum electrostatics. For each system, the following quantities are reported: the net charge Q_P of the protein; the net charge Q_I of the counter-ion atmosphere; the minimal and maximal edge lengths L_min and L_max of the box (incremented in steps of about 0.4 nm; see Table 2 for the individual values); the corresponding minimal and maximal numbers N_S,min and N_S,max of freely moving water molecules (see Table 2 for the individual values); the number N_B of bound (fixed coordinates) water molecules (see Sec. 3A); the numbers N_Na,max and N_Cl,max of sodium and chloride counter-ions included in the largest box of edge L_max; the ionic strength I_str of the system; the inverse Debye screening length κ of the system. For the systems with counter-ions, the number of ions was adjusted to enforce Q_I = −Q_P and to keep I_str and κ approximately constant across the different box-edge lengths. The ligand charge is Q_L = +1 e in all cases. More detailed information on the simulated systems as well as the raw simulation results can be found in Table S1 of the supplementary material.¹⁵⁴

System	QP (e)	QI (e)	Lmin (nm)	Lmax (nm)	NS,min	NS,max	NB	NNa,max	NCl,max	Istr (mol kg−1)	κ (nm−1)
lig	0	0	3.05	13.50	928	80 897	0	0	0	0	0
net-5	−5	0	7.42	11.02	12 077	43 591	69	0	0	0	0
net0	0	0	7.42	13.02	12 077	72 810	69	0	0	0	0
net3	3	0	7.42	11.02	12 077	43 591	69	0	0	0	0
net9	9	0	7.42	11.02	12 077	43 591	69	0	0	0	0
net9quad	9	0	7.42	11.02	12 077	43 591	69	0	0	0	0
net-5ion	−5	5	7.42	11.02	12 022	43 424	69	86	81	∼0.1	∼1.0
net9ion	9	−9	7.42	11.02	12 017	43 419	69	81	90	∼0.1	∼1.0