For all simulation systems, the interactions were modeled using the CHARMM36 allatom force field 42 with dihedral modifications for improved sampling of the amino acid side chain rotamers. This modified force field already contains the entries for the titratable Glu, Asp and His, as well as the buffer particle. 27,28 To prepare the system for cardiotoxin V and the barnase-barstar complex (either prior or while applying phbuilder), the following procedure was used: (1) the corresponding .pdb file was obtained from the Protein Data Bank, (2) the protein was placed in a cubic box with a 2.0 nm distance between the protein and the box, (3) the system was solvated with ≈17000 CHARMM TIP3P waters for cardiotoxin V and ≈31000 for barnase-barstar, and