Tunneling and nonadiabatic effects on a PCET model for the Qo site in cytochrome bc1

CAMILO, SOFÍA; CURTOLO, FELIPE; GALASSI, VANESA V.; GUILHERME MENEGON ARANTES

JOURNAL OF CHEMICAL INFORMATION AND MODELING

AMER CHEMICAL SOC

Año: 2021

1549-9596

Cytochromebc1isa fundamental enzyme for cellular respiration and photosynthesis.This dimeric protein complex catalyzes a proton-coupled electrontransfer (PCET) from the re- duced coenzyme-Q substrate (Q) to abi-metallic iron-sulfur cluster in the Qoactivesite. Herein, we combine molecular dynamics simulations of thecomplete bc1proteinwith electronic- structure calculations of truncated models and asemiclassical tunneling theory to investigate the electron-protonadiabaticity of the initial reaction catalyzed in the Qosite.After sampling possible orientations between the Q substrate and ahistidine side-chain that function as hydrogen acceptor, we find thata truncated model composed by ubiquinol-methyl and imidazole-iron(III)-sulfide captures the expected changes in oxidation and spinstates of electron donor (Q-head) and acceptor (iron-sulfur center)along the proton transfer reaction. Diabatic electronic surfacesobtained for this model with multiconfigurational wave-function calculations are analyzed to show this reaction is electronicnonadiabatic and proton tunneling is faster than mixing of electronicconfigurations. These results indicate the theoretical formalismthat should be used to calculate kinetic parameters for the initialreaction in the Qositeand suggest a molecular simulation framework that may be applied toinves- tigate other PCET reactions in the Q-cycle or in variousmetalloproteins that catalyze proton translocation coupled to redoxprocesses. p { margin-bottom: 0.1in; line-height: 115% }