The original and modified (described in detail below) CHARMM36m force fields were used in all simulations. The table also presents the box size, the number of CHARMM36 TIP3P water molecules, ions, and buffer particles included in each system. The fitting coefficients of the V MM correction potential for the buffer particles were obtained with system BUF 1 . To find the optimal charge range and Lennard-Jones parameters for the buffer particles, the enhanced sampling simulations with the accelerated weight histogram (AWH) method were performed on system BUF 2 . Systems ADA, AEA, AKA, and AHA are alanine tripeptides with capped termini, and as central residue aspartic, glutamic, lysine, and histidine amino acids, respectively. AAA 1 and AAA 2 systems are alanine tripeptides with protonated termini. C-and N-termini were made titratable in AAA 1 and AAA 2 systems, respectively. Two sets of simulations of the cardiotoxin V protein were performed. System 1CVO 1 was used to calculate the pK a values of titratable residues, while the larger system 1CVO 2 was used to compute the radial distribution function of the buffer particles around the protein. The membrane systems MEMB 1 and MEMB 2 contained 106 1-palmitoyl-2oleoyl-glycero-3-phosphocholine (POPC) lipids. Starting coordinates and topologies of all systems are provided as Supporting Information.