Electron transport is the essential mechanism for energy flow in respiration and photosynthesis. The mechanisms for electron transfer by proteins are still the subject of much debate. The research proposed here is to study electron transfer proteins by computational techniques such as molecular dynamics simulations. In these methods, the motions of individual atoms in a protein are modeled. This research is aimed at simulations of iron-sulfur proteins, which are a class of electron transfer proteins which are well characterized experimentally but not by simulations. Most of the initial studies will focus on the rubredoxins, which have a single iron. Preliminary steps will involve simple studies of the structure and dynamics of rubredoxin via molecular dynamics simulations. The next step will be to study how the protein environment influences the iron-sulfur site. The magnitudes and fluctuations of the distances the electron must travel and the polarization field at the active site can be calculated from the simulation. Comparison with simulations of analogs of the active site in solution can provide insight into how the protein environment alters the transfer process from what it would be for a simple compound with the same iron-sulfur site. Also, simulations of homologous rubredoxins, for which there are x-ray structures, can be used to determine how specific amino acid changes can influence the transfer. The eventual goal will be to develop methods for studying the quantum mechanical phenomena of electron transfer. One study will involve using path integral simulations of the transfer electron in the environment of the protein. Another approach will be to consider electron transfer as a two-level system. In this case, an important quantity to calculate is the interaction energy between the protein environment and the electron density (in the wavefunction representation of the electron) in the oxidized and reduced states.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
1R29GM045303-01A1
Application #
3468302
Study Section
Molecular and Cellular Biophysics Study Section (BBCA)
Project Start
1992-02-01
Project End
1997-01-31
Budget Start
1992-02-01
Budget End
1993-01-31
Support Year
1
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Washington State University
Department
Type
Schools of Arts and Sciences
DUNS #
041485301
City
Pullman
State
WA
Country
United States
Zip Code
99164
Perrin Jr, B Scott; Miller, Benjamin T; Schalk, Vinushka et al. (2014) Web-based computational chemistry education with CHARMMing III: Reduction potentials of electron transfer proteins. PLoS Comput Biol 10:e1003739
Perrin Jr, Bradley Scott; Niu, Shuqiang; Ichiye, Toshiko (2013) Calculating standard reduction potentials of [4Fe-4S] proteins. J Comput Chem 34:576-82
Luo, Yan; Niu, Shuqiang; Ichiye, Toshiko (2012) Understanding rubredoxin redox sites by density functional theory studies of analogues. J Phys Chem A 116:8918-24
Mitra, Devrani; Pelmenschikov, Vladimir; Guo, Yisong et al. (2011) Dynamics of the [4Fe-4S] cluster in Pyrococcus furiosus D14C ferredoxin via nuclear resonance vibrational and resonance Raman spectroscopies, force field simulations, and density functional theory calculations. Biochemistry 50:5220-35
Luo, Yan; Ergenekan, Can E; Fischer, Justin T et al. (2010) The molecular determinants of the increased reduction potential of the rubredoxin domain of rubrerythrin relative to rubredoxin. Biophys J 98:560-8
Perrin Jr, Bradley Scott; Ichiye, Toshiko (2010) Fold versus sequence effects on the driving force for protein-mediated electron transfer. Proteins 78:2798-808
Niu, Shuqiang; Ichiye, Toshiko (2009) Insight into environmental effects on bonding and redox properties of [4Fe-4S] clusters in proteins. J Am Chem Soc 131:5724-5
Niu, Shuqiang; Ichiye, Toshiko (2009) Probing ligand effects on the redox energies of [4Fe-4S] clusters using broken-symmetry density functional theory. J Phys Chem A 113:5671-6
Niu, Shuqiang; Nichols, Jeffrey A; Ichiye, Toshiko (2009) Optimization of Spin-Unrestricted Density Functional Theory for Redox Properties of Rubredoxin Redox Site Analogues. J Chem Theory Comput 5:1361-1368
Niu, Shuqiang; Ichiye, Toshiko (2009) Cleavage of [4Fe-4S]-type clusters: breaking the symmetry. J Phys Chem A 113:5710-7

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