The protonation states and hydrogen positions obtained from these NMR ensemble structures were used as a starting point for all simulations (Supporting Information Table ). Three residues differ between Trp-cage TC5b[117] and its TC10b mutant[118]: Asn1, Leu2, and Ile4 in the former are replaced by Asp1, Ala2, and Ala4 in the latter (Figure ). As a result, the net charge of TC5b is +1, whereas TC10b has a net charge of 0 (Supporting Information Table ).