TY - JOUR
T1 - Theory of Protein Charge Transfer
T2 - Electron Transfer between Tryptophan Residue and Active Site of Azurin
AU - Sarhangi, Setare Mostajabi
AU - Matyushov, Dmitry V.
N1 - Funding Information:
This research was supported by the Army Research Office (ARO-W911NF2010320) and by the National Science Foundation (CHE-2154465). The supercomputer time was provided through Extreme Science and Engineering Discovery Environment (XSEDE) allocation MCB080071 and through ASU’s Research Computing.
Publisher Copyright:
© 2022 American Chemical Society.
PY - 2022/12/15
Y1 - 2022/12/15
N2 - 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 nonparabolic 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, where 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.
AB - 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 nonparabolic 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, where 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.
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U2 - 10.1021/acs.jpcb.2c05258
DO - 10.1021/acs.jpcb.2c05258
M3 - Article
C2 - 36459590
AN - SCOPUS:85144447789
SN - 1520-6106
VL - 126
SP - 10360
EP - 10373
JO - Journal of Physical Chemistry B
JF - Journal of Physical Chemistry B
IS - 49
ER -