Electron Transfer in Proteins: Structural and Energetic Control of the Electronic Coupling Jose ´ -Maria Lopez-Castillo, Abdelali Filali-Mouhim, E Ä lise Nguyen Van Binh-Otten, and Jean-Paul Jay-Gerin* Contribution from the Groupe du Conseil de Recherches Me ´ dicales du Canada en Sciences des Radiations, De ´ partement de Me ´ decine Nucle ´ aire et de Radiobiologie, Faculte ´ de Me ´ decine, UniVersite ´ de Sherbrooke, Sherbrooke (Que ´ bec) J1H 5N4, Canada ReceiVed June 12, 1996 X Abstract: The available experimental data on the electron donor (D)-acceptor (A) coupling (H DA ) for electron- transfer (ET) reactions in proteins are re-examined. In spite of their structural and energetic similarities, the photosynthetic reaction center and other ET protein systems exhibit a marked difference of the exponential decay of H DA with the distance separating D and A. A numerical study shows that this difference is explained in terms of very small variations of the energetics between these two classes of proteins. Since the proposal of Dutton and co-workers 1 of a “universal” relationship between the electron donor (D)-acceptor (A) coupling (H DA ) and the distance (d) separating D and A in electron-transfer (ET) proteins, a number of experiments have shown important departures from such a simple picture. 2 The situation has come to a tendency toward a classification of ET proteins into two groups, according to their ability to fit or not to fit the “universal” law. 3,4 Proteins of the “universal” type seem to conform to a one-dimensional square-barrier (1DSB) model, for which Gamow’s formula gives an exponential dependence of H DA on d, with a decay constant 1DSB ) (2mE/ p 2 ) 1/2 , where m is the electron mass, p is Planck’s constant divided by 2π, and E is the energy of the tunneling electron. Dutton’s compilation 1 gives 1DSB ) 0.7 Å -1 from the average exponential decay of the maximum ET rate constant k max (s -1 ) ) 10 13 e -1.4(d-3.6) Versus d (Å). Other ET proteins do not show such a simple correlation of H DA with d. Instead, there seems to be a more pronounced correlation of H DA with the length of some specific pathways from D to A, along the protein bonds. Onuchic and Beratan and co-workers 5 (OB) associated to each of these pathways an additive contribution to H DA allowing for a selection of those with the optimum coupling strengths. The limitations of both theories are well-known. Briefly, Dutton’s model simply does not rely upon a microscopic description of proteins, while, as we will show below, OB’s approximation largely underestimates the contributions of through-space (TS) interactions. An accurate determination of H DA must include the complete structural and energetic com- plexity of proteins into the electronic Hamiltonian, which has to be treated exactly. 6 To date, only a very limited number of such studies exists. 7 It is therefore difficult to appreciate the whole behavior of H DA in ET proteins. A lucid discussion of the present status of the theory has been given by Friesner. 8 In this paper, we re-examine the available experimental data, including the most recent ones, on the k max -Vs-d correlation. Our compilation clearly distinguishes between the photosynthetic reaction center (PRC) and other ET protein systems. By analyzing, on a variety of proteins, the possible energetic and structural origins of the observed behaviors, we show that there is no influence of the protein’s structure on the aVerage distance-decay rate of H DA . However, experimental data support the notion of a large dispersion of the electronic energy levels of the protein as reflected by the important scatter of the data. According to theory, k max is related to H DA through the semiclassical Marcus expression for the ET rate constant k: 9 where k B is the Boltzmann constant, T is the temperature, λ is the nuclear reorganization energy accompanying ET, and ΔG° is the reaction free-energy change. k max is reached at vanishing activation energy (G° )-λ), where the numerical estimate of k max (in s -1 ) as a function of H DA (in cm -1 ) holds for a typical reorganization energy λ ) 1 eV at T ) 300 K. H DA reflects the influence of the intervening medium on the ET rate. Table 1 presents an up-to-date compilation of k max Versus d for 23 ET protein systems studied in the literature. 10-20 These Present address: Service de Ge ´ne ´tique Me ´dicale, Ho ˆpital Sainte-Justine, 3175, Chemin Co ˆte Sainte-Catherine, Montre ´al (Que ´bec) H3T 1C5, Canada. X Abstract published in AdVance ACS Abstracts, February 1, 1997. (1) Moser, C. C.; Keske, J. M.; Warncke, K.; Farid, R. S.; Dutton, P. L. Nature 1992, 355, 796-802. (2) Beratan, D. N.; Onuchic, J. N.; Winkler, J. R.; Gray, H. B. Science 1992, 258, 1740-1741 and references therein. (3) Evenson, J. W.; Karplus, M. Science 1993, 262, 1247-1249. (4) Farid, R. S.; Moser, C. C.; Dutton, P. L. Curr. Opin. Struct. Biol. 1993, 3, 225-233. (5) Onuchic, J. N.; Beratan, D. N.; Winkler, J. R.; Gray, H. B. Annu. ReV. Biophys. Biomol. Struct. 1992, 21, 349-377 and references therein. Betts, J. N.; Beratan, D. N.; Onuchic, J. N. J. Am. Chem. Soc. 1992, 114, 4043-4046. Regan, J. J.; Risser, S. M.; Beratan, D. N.; Onuchic, J. N. J. Phys. Chem. 1993, 97, 13083-13088. Skourtis, S. S.; Regan, J. J.; Onuchic, J. N. J. Phys. Chem. 1994, 98, 3379-3388. (6) Stuchebrukhov, A. A.; Marcus, R. A. J. Phys. Chem. 1995, 99, 7581- 7590. Stuchebrukhov, A. A. Chem. Phys. Lett. 1994, 225, 55-61. (7) Kuki, A.; Wolynes, P. G. Science 1987, 236, 1647-1652. Gruschus, J. M.; Kuki, A. J. Phys. Chem. 1993, 97, 5581-5593. Siddarth, P.; Marcus, R. A. J. Phys. Chem. 1993, 97, 13078-13082 and references therein. Okada, A.; Kakitani, T.; Inoue, J. J. Phys. Chem. 1995, 99, 2946-2948. (8) Friesner, R. A. Structure 1994, 2, 339-343. (9) Marcus, R. A.; Sutin, N. Biochim. Biophys. Acta 1985, 811, 265- 322. (10) McLendon, G.; Miller, J. R. J. Am. Chem. Soc. 1985, 107, 7811- 7816. k ) 2π p |H DA | 2 1 4πλk B T e -(G°+λ) 2 /4λk B T (1) k max ) 2π p |H DA | 2 1 4πλk B T (2.575 × 10 8 )|H DA | 2 (2) 1978 J. Am. Chem. Soc. 1997, 119, 1978-1980 S0002-7863(96)01978-6 CCC: $14.00 © 1997 American Chemical Society