Proton-regulated electron transfers from tyrosine to tryptophan in proteins: through-bond mechanism versus long-range hopping mechanism.

Charge transfer between tyrosine and tryptophan residues in proteins is continuously a hot topic because of its important biological implication. On the basis of DFT calculations and ab initio molecular dynamics simulations, several possible proton/electron cooperative transfer mechanisms from tyrosine to a tryptophan radical (or cation) without or with the assistence of a base in proteins are proposed in this work which range from direct proton-coupled pi-electron pi-channel/sigma-channel transfers (PC(pi)E(pi)T versus PC(pi)E(sigma)T) to proton-coupled long-range hopping mechanisms depending on the peptide conformations. In general, because of a smaller ionization potential, tryptophan readily behaves as two oxidized states: dehydrogenated neutral radical and ionized radical cation. For the neutral radical, the proton/electron transfers between a tyrosine and a tryptophan radical prefer a cooperative direct coupling mode through the PC(pi)E(pi)T or PC(pi)E(sigma)T mechanism if two residues are proximal or can approach each other, while they cannot take place without assistence if two residues are far apart. The tryptophan radical cation prefers to form a complex with tyrosine to stabilize the hole when two residues are proximal or can approach each other. However, the electron transfer from tyrosine to tryptophan could occur via a hopping mechanism but is regulated by a base as a proton acceptor in the vicinity of tyrosine when two residues are separated. The dynamics properties and characters for these transfer events are also presented. The energetics comparison indicates that the energy barriers for the direct PCET (PC(pi)E(pi)T or PC(pi)E(sigma)T) mechanisms are higher than those of the base-assisting hopping mechanism (6.8-12.5 versus <or=4.9 kcal/mol), implying the latter is a favorable way for the proton/electron cooperative transfers. Hopefully, this work provides some helpful information for understanding the mechanisms of physiologically important electron transfer reactions.