The reaction free energies and associated pK(a) values for proton transfer from positively charged tryptophan (HTrp(+)) to the two pure ionic liquids (ILs) BMIM-PF6 and BMIM-BF4 are derived from molecular simulations. IL solvation effects are examined with molecular dynamics simulations together with an empirical force field in which the average charge distribution in the actual IL is taken into account. A combination of molecular mechanical and quantum mechanical description (QM/MM) is used to examine the protonation of the anion constituents of the ILs. A dissociation of the protonated anions is observed into hydrogen fluoride and BF3 or PF5. Finally, pK(a) values of 16.5 and 21.5 in BMIM-BF4 and BMIM-PF6, respectively, are found for proton transfer from HTrp(+) to PF6(-) and BF4(-) anions, which indicates that a deprotonation of HTrp(+) is highly unfavorable compared to aqueous solutions. An examination of the contributions to the reaction free energies demonstrates that a deprotonation of tryptophan is impeded because two ions need to be annihilated for the reaction to occur: HTrp(+) and an anion. While the solvation effects induced by the two ILs are similar, the low proton acceptance of PF6(-) anions leads to the larger pK(a) value in BMIM-PF6. Also, estimates suggest that IL-induced pK(a) shifts are comparably small in proton transfer reactions where the total number of ions remains unchanged. For the first time, pK(a) values of acids were determined computationally in ILs. The obtained results elucidate the role of solvation effects on proton transfer between amino acids and ILs and improve our understanding of the observed pH memory of proteins that are solvated in ILs.