Proton affinity of the histidine-tryptophan cluster motif from the influenza A virus fromab initiomolecular dynamics.
Ab initiomolecular dynamics calculations have been used to compare and contrast the deprotonation reaction of a histidine residue in aqueous solution with the situation arising in a histidine-tryptophan cluster. The latter is used as a model of the proton storage unit present in the pore of the M2 proton conducting ion channel. We compute potentials of mean force for the dissociation of a proton from the Nδand Nεpositions of the imidazole group to estimate the pKa's.Anticipating our results, we will see that the estimated pKafor the first protonation event of the M2 channel is in good agreement with experimental estimates. Surprisingly, despite the fact that the histidine is partially desolvated in the M2 channel, the affinity for protons is similar to that of a histidine in aqueous solution. Importantly, the electrostatic environment provided by the indoles is responsible for the stabilization of the charged imidazolium.
Institute for Computational Molecular Science, Temple University, Philadelphia, Pennsylvania 19122, United States.
Arindam
A
Bankura
Institute for Computational Molecular Science, Temple University, Philadelphia, Pennsylvania 19122, United States.
Michael L
ML
Klein
Institute for Computational Molecular Science, Temple University, Philadelphia, Pennsylvania 19122, United States.
Vincenzo
V
Carnevale