Theory of Protein Charge Transfer: Electron Transfer between Tryptophan Residue and Active Site of Azurin

Abstract

One reaction step in the conductivity relay of azurin, electron transfer between the Cu-based active site and the tryptophan residue, is studied theoretically and by classical molecular dynamics simulations. Oxidation of tryptophan results in electrowetting of this residue. This structural change makes the free energy surfaces of electron transfer non-parabolic as described by the Q-model of electron transfer. We analyze the medium dynamical effect on protein electron transfer produced by coupled Stokes-shift dynamics and the dynamics of the donor-acceptor distance modulating electron tunneling. The equilibrium donor-acceptor distance falls in the plateau region of the rate constant, when it is determined by the protein-water dynamics and the probability of electron tunneling does not affect the rate. The crossover distance found here puts most intraprotein electron-transfer reactions under the umbrella of dynamical control. The crossover between the medium-controlled and tunneling-controlled kinetics is combined with the effect of the protein-water medium on the activation barrier to formulate principles of tunability of protein-based charge-transfer chains. The main principle in optimizing the activation barrier is the departure from the Gaussian-Gibbsian statistics of fluctuations promoting activated transitions. This is achieved either by incomplete (nonergodic) sampling, breaking the link between the Stokes-shift and variance reorganization energies, or through wetting-induced structural changes of the enzyme's active site.

Electron Tunneling in Biology: When Does it Matter?

“…The average distance between tyrosine's phenol ring and the Cu atom of the active site ⟨R⟩ i changes somewhat between the two states, but the main difference between two electron-transfer states in terms of distance statistics is in the distance variance. Consistently with our previous simulations of wild type azurine [57], the state with a higher number of water molecules around the residue shows a greater extend of distance flexibility. In the present simulations, a larger number of water molecules was found around neutral Tyr (Figure S10), which is reflected by a broader distribution of donor-acceptor distanced (Figure S3) and a larger distance variance (Table 1).…”

“…The present article extends our previous results [57] for intraprotein electron transfer between tryptophan (Trp) residue of azurin and its active site to a single-residue mutation replacing tryptophan with tyrozine (Tyr). The reaction of transferring the hole from Trp to Cu I of the active site was studied experimentally by Shih et al [58] and the reaction time of τ ET ≃ 31 ns reported.…”

“…( 8) accounting for the nonadiabatic rate constant k NA and the dynamical crossover parameter making the reaction rate independent of the distance in the dynamically controlled regime. The nonadibatic rate constant was calculated as elsewhere [57] by using the electronic coupling V e (Eq. ( 5)) provided by Voityuk [68] (see SM).…”

Effect of water deuteration on protein electron transfer

“…Molecular dynamics (MD) simulation and theoretical calculations presented in this Letter support this hypothesis. Here and elsewhere 31 we use MD simulations to study the activation parameters of transferring a hole from the tryptophan (Trp + ) cation radical to Cu I active site of azurin 32…”

“…MD simulations were set up as described elsewhere 31 and in Supplementary Information (SI). Briefly, azurin protein in two electron-transfer states was solvated with 36469 TIP3P/TIP3P-HW (Table 1) water molecules and the production simulations of 300 ns were done in the NVT ensemble.…”