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Photoinduced hole hopping through tryptophans in proteins

Záliš, Stanislav and Heyda, Jan and Šebesta, Filip and Winkler, Jay R. and Gray, Harry B. and Vlček, Antonín (2021) Photoinduced hole hopping through tryptophans in proteins. Proceedings of the National Academy of Sciences of the United States of America, 118 (11). Art. No. e2024627118. ISSN 0027-8424. PMCID PMC7980458.

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Hole hopping through tryptophan/tyrosine chains enables rapid unidirectional charge transport over long distances. We have elucidated structural and dynamical factors controlling hopping speed and efficiency in two modified azurin constructs that include a rhenium(I) sensitizer, Re(His)(CO)₃(dmp)⁺, and one or two tryptophans (W₁, W₂). Experimental kinetics investigations showed that the two closely spaced (3 to 4 Å) intervening tryptophans dramatically accelerated long-range electron transfer (ET) from Cu^I to the photoexcited sensitizer. In our theoretical work, we found that time-dependent density-functional theory (TDDFT) quantum mechanics/molecular mechanics/molecular dynamics (QM/MM/MD) trajectories of low-lying triplet excited states of Re^I(His)(CO)₃(dmp)⁺–W₁(–W₂) exhibited crossings between sensitizer-localized (*Re) and charge-separated [Re^I(His)(CO)₃(dmp•–)/(W₁•+ or W₂•+)] (CS1 or CS2) states. Our analysis revealed that the distances, angles, and mutual orientations of ET-active cofactors fluctuate in a relatively narrow range in which the cofactors are strongly coupled, enabling adiabatic ET. Water-dominated electrostatic field fluctuations bring *Re and CS1 states to a crossing where *Re(CO)₃(dmp)⁺←W₁ ET occurs, and CS1 becomes the lowest triplet state. ET is promoted by solvation dynamics around *Re(CO)₃(dmp)⁺(W₁); and CS1 is stabilized by Re(dmp•–)/W₁•+ electron/hole interaction and enhanced W₁•+ solvation. The second hop, W₁•+←W₂, is facilitated by water fluctuations near the W₁/W₂ unit, taking place when the electrostatic potential at W₂ drops well below that at W₁•+. Insufficient solvation and reorganization around W₂ make W₁•+←W₂ ET endergonic, shifting the equilibrium toward W₁•+ and decreasing the charge-separation yield. We suggest that multiscale TDDFT/MM/MD is a suitable technique to model the simultaneous evolution of photogenerated excited-state manifolds.

Item Type:Article
Related URLs:
URLURL TypeDescription Information
Záliš, Stanislav0000-0003-4345-3205
Heyda, Jan0000-0002-9428-9508
Šebesta, Filip0000-0001-6707-8118
Winkler, Jay R.0000-0002-4453-9716
Gray, Harry B.0000-0002-7937-7876
Vlček, Antonín0000-0002-6413-8311
Additional Information:© 2021 National Academy of Sciences. Published under the PNAS license. Contributed by Harry B. Gray, January 28, 2021 (sent for review December 1, 2020; reviewed by David N. Beratan and Jochen Blumberger). This work was supported by Czech Ministry of Education Youth and Sports (MŠMT) Grant LTAUSA18026, Engineering and Physical Sciences Research Council Grant (United Kingdom) EP/R029687/1, and the National Institute of Diabetes and Digestive and Kidney Diseases of the NIH under Award R01DK019038. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Computational resources were provided by the Czech IT4-Innovations National Supercomputing Center (OPEN-20-8) and MetaCentrum through the MŠMT project Large Infrastructures for Research, Experimental Development and Innovations “e-Infrastructure CZ – LM2018140.” Data Availability: All study data are included in the article and/or SI Appendix. Author contributions: S.Z., J.H., and A.V. designed research; S.Z., J.H., and F.S. performed research; S.Z., J.H., F.S., J.R.W., H.B.G., and A.V. analyzed data; and H.B.G. and A.V. wrote the paper. Reviewers: D.N.B., Duke University; and J.B., University College London. The authors declare no competing interest. This article contains supporting information online at
Funding AgencyGrant Number
Ministerstvo Školství, Mládeže a TělovýchovyLTAUSA18026
Engineering and Physical Sciences Research Council (EPSRC)EP/R029687/1
Subject Keywords:electron transfer; hole hopping; azurin; tryptophan; molecular dynamics
Issue or Number:11
PubMed Central ID:PMC7980458
Record Number:CaltechAUTHORS:20210308-152531374
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Official Citation:Photoinduced hole hopping through tryptophans in proteins. Stanislav Záliš, Jan Heyda, Filip Šebesta, Jay R. Winkler, Harry B. Gray, Antonín Vlček. Proceedings of the National Academy of Sciences Mar 2021, 118 (11) e2024627118; DOI: 10.1073/pnas.2024627118
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:108350
Deposited By: Tony Diaz
Deposited On:08 Mar 2021 23:39
Last Modified:19 Apr 2021 17:15

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