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Interfacial hydration, dynamics and electron transfer: multi-scale ET modeling of the transient [myoglobin, cytochrome b5] complex.

Publication ,  Journal Article
Keinan, S; Nocek, JM; Hoffman, BM; Beratan, DN
Published in: Physical chemistry chemical physics : PCCP
October 2012

Formation of a transient [myoglobin (Mb), cytochrome b(5) (cyt b(5))] complex is required for the reductive repair of inactive ferri-Mb to its functional ferro-Mb state. The [Mb, cyt b(5)] complex exhibits dynamic docking (DD), with its cyt b(5) partner in rapid exchange at multiple sites on the Mb surface. A triple mutant (Mb(3M)) was designed as part of efforts to shift the electron-transfer process to the simple docking (SD) regime, in which reactive binding occurs at a restricted, reactive region on the Mb surface that dominates the docked ensemble. An electrostatically-guided brownian dynamics (BD) docking protocol was used to generate an initial ensemble of reactive configurations of the complex between unrelaxed partners. This ensemble samples a broad and diverse array of heme-heme distances and orientations. These configurations seeded all-atom constrained molecular dynamics simulations (MD) to generate relaxed complexes for the calculation of electron tunneling matrix elements (T(DA)) through tunneling-pathway analysis. This procedure for generating an ensemble of relaxed complexes combines the ability of BD calculations to sample the large variety of available conformations and interprotein distances, with the ability of MD to generate the atomic level information, especially regarding the structure of water molecules at the protein-protein interface, that defines electron-tunneling pathways. We used the calculated T(DA) values to compute ET rates for the [Mb(wt), cyt b(5)] complex and for the complex with a mutant that has a binding free energy strengthened by three D/E → K charge-reversal mutations, [Mb(3M), cyt b(5)]. The calculated rate constants are in agreement with the measured values, and the mutant complex ensemble has many more geometries with higher T(DA) values than does the wild-type Mb complex. Interestingly, water plays a double role in this electron-transfer system, lowering the tunneling barrier as well as inducing protein interface remodeling that screens the repulsion between the negatively-charged propionates of the two hemes.

Duke Scholars

Published In

Physical chemistry chemical physics : PCCP

DOI

EISSN

1463-9084

ISSN

1463-9076

Publication Date

October 2012

Volume

14

Issue

40

Start / End Page

13881 / 13889

Related Subject Headings

  • Water
  • Protein Interaction Mapping
  • Myoglobin
  • Mutation
  • Molecular Docking Simulation
  • Horses
  • Electrons
  • Electron Transport
  • Cytochromes b5
  • Chemical Physics
 

Citation

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Keinan, S., Nocek, J. M., Hoffman, B. M., & Beratan, D. N. (2012). Interfacial hydration, dynamics and electron transfer: multi-scale ET modeling of the transient [myoglobin, cytochrome b5] complex. Physical Chemistry Chemical Physics : PCCP, 14(40), 13881–13889. https://doi.org/10.1039/c2cp41949a
Keinan, Shahar, Judith M. Nocek, Brian M. Hoffman, and David N. Beratan. “Interfacial hydration, dynamics and electron transfer: multi-scale ET modeling of the transient [myoglobin, cytochrome b5] complex.Physical Chemistry Chemical Physics : PCCP 14, no. 40 (October 2012): 13881–89. https://doi.org/10.1039/c2cp41949a.
Keinan S, Nocek JM, Hoffman BM, Beratan DN. Interfacial hydration, dynamics and electron transfer: multi-scale ET modeling of the transient [myoglobin, cytochrome b5] complex. Physical chemistry chemical physics : PCCP. 2012 Oct;14(40):13881–9.
Keinan, Shahar, et al. “Interfacial hydration, dynamics and electron transfer: multi-scale ET modeling of the transient [myoglobin, cytochrome b5] complex.Physical Chemistry Chemical Physics : PCCP, vol. 14, no. 40, Oct. 2012, pp. 13881–89. Epmc, doi:10.1039/c2cp41949a.
Keinan S, Nocek JM, Hoffman BM, Beratan DN. Interfacial hydration, dynamics and electron transfer: multi-scale ET modeling of the transient [myoglobin, cytochrome b5] complex. Physical chemistry chemical physics : PCCP. 2012 Oct;14(40):13881–13889.
Journal cover image

Published In

Physical chemistry chemical physics : PCCP

DOI

EISSN

1463-9084

ISSN

1463-9076

Publication Date

October 2012

Volume

14

Issue

40

Start / End Page

13881 / 13889

Related Subject Headings

  • Water
  • Protein Interaction Mapping
  • Myoglobin
  • Mutation
  • Molecular Docking Simulation
  • Horses
  • Electrons
  • Electron Transport
  • Cytochromes b5
  • Chemical Physics