We will study proton-coupled electron transfer (PCET) reactions and proton translocation (PTR) with the goal of understanding energy conversion in the Photosystem II Oxygen Evolving Complex and cytochrome c oxidase (CcO). These two metalloenzymes form an important part of the biochemical oxygen cycle, and it is well appreciated that both rely on PCET and PTR for their energy transduction function. Both photosynthesis and oxidative phosphorylation couple the movement of electrons and protons across a membrane to the generation of an electrochemical proton gradient. These gradients are used to generate ATP and provide the energy """"""""currency"""""""" for biosynthesis. If the process is defective, with a membrane that cannot maintain an electrochemical proton gradient, ATP is no longer synthesized. Many diseases associated with aging are related to deficiencies in the operation of CcO. As mitochondrial mutations accumulate, damage to the electron transfer mechanism occurs, and oxygen radicals, that are implicated in the aging process, accumulate. Theories that couple the transfer of electrons and protons together are not well developed, and will be a goal of this research. We will obtain formal expressions for the rates of PCET reactions and, with suitable numerical schemes, evaluate the parameters that enter these rate expressions, to make quantitative predictions of rates and mechanisms for PCET. These PCET events are intimately connected with the transport of protons through membrane-bound proteins; consequently, theories of PTR are the other goal of this research. We will develop theoretical methods that permit the description of proton transport through hydrogen-bonded water and residue pathways. Contemporaneously, we will explore PTR by simulation methodologies that we are developing, which combine quantum mechanics and molecular dynamics to quantitatively describe proton translocation.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM062790-02
Application #
6520436
Study Section
Metallobiochemistry Study Section (BMT)
Program Officer
Preusch, Peter C
Project Start
2001-06-01
Project End
2005-05-31
Budget Start
2002-06-01
Budget End
2003-05-31
Support Year
2
Fiscal Year
2002
Total Cost
$123,636
Indirect Cost
Name
Michigan State University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824
Chen, Xiaohua; Xing, Dianxiang; Zhang, Liang et al. (2009) Effect of metal ions on radical type and proton-coupled electron transfer channel: sigma-radical vs pi-radical and sigma-channel vs pi-channel in the imide units. J Comput Chem 30:2694-705
Han, Li; Li, Huifang; Cukier, Robert I et al. (2009) Hetero-ring-expansion design for adenine-based DNA motifs: evidence from DFT calculations and molecular dynamics simulations. J Phys Chem B 113:4407-12
Zhang, Liang; Yan, Shihai; Cukier, R I et al. (2008) Solvation of excess electrons in LiF ionic pair matrix: evidence for a solvated dielectron from ab initio molecular dynamics simulations and calculations. J Phys Chem B 112:3767-72
Xing, Dianxiang; Bu, Yuxiang; Tan, Xuejie (2008) Characterizing the properties of the N7,N9-dimethylguaninium chloride ion pairs: prospecting for the design of a novel ionic liquid. J Phys Chem A 112:106-16
Li, Huifang; Cukier, Robert I; Bu, Yuxiang (2008) Remarkable metal counterion effect on the internucleotide J-couplings and chemical shifts of the N-H...N hydrogen bonds in the W-C base pairs. J Phys Chem B 112:9174-81
Su, Li; Cukier, Robert I (2007) Hamiltonian and distance replica exchange method studies of Met-enkephalin. J Phys Chem B 111:12310-21
Xiang, Feng; Cukier, Robert I; Bu, Yuxiang (2007) Ca2+ selectivity of the sarcoplasmic reticulum Ca2+-ATPase at the enzyme-water interface and in the Ca2+ entrance channel. J Phys Chem B 111:12282-93
Zhang, Jinmei; Cukier, Robert I; Bu, Yuxiang (2007) Rational design of hetero-ring-expanded guanine analogs with enhanced properties for modified DNA building blocks. J Phys Chem B 111:8335-41
Sun, Lixiang; Cukier, Robert I; Bu, Yuxiang (2007) Factors determining the deriving force of DNA formation: geometrical differences of base pairs, dehydration of bases, and the arginine assisting. J Phys Chem B 111:1802-8
Yan, Shihai; Zhang, Liang; Cukier, Robert I et al. (2007) Exploration on regulating factors for proton transfer along hydrogen-bonded water chains. Chemphyschem 8:944-54

Showing the most recent 10 out of 17 publications