Electronic Transfer Calculations for the Hemes of Flavocytochrome c3
EMSL Project ID
2628
Abstract
As part of the DOE Office of Science Program Notice 01-21 for Advanced Modeling and Simulation of Biological Systems, we have received funding for development of new large-scale electron transfer simulation tools. As a case-in-point, we are modeling the complex enzymatic reactions involved in the respiratory cycle of iron-reducing bacteria. The goal of this work is to provide the computational tools required for a detailed molecular-level characterization and understanding of intricate biological reactions such as the electron transfer through flavocytochrome c3 (Ifc3) of Shewanella frigidimarina, our prototypical case. Though the scope of the full project merits a grand challenge, we have broken up the initial research into several pilot projects that will provide guidance for a future grand challenge proposal. One of the major objectives of the proposed research is to obtain a detailed theoretical characterization of the electronic structure and reductive function of the redox center of Ifc3 in S. frigidamarina by applying advanced quantum mechanical methods. We recently met this objective and submitted a publication to the Journal of the American Chemical Society detailing our DFT study of a bis(histidine) heme model complex. The paper includes the optimized geometries, relative energies, Fe(3d) orbital population analysis, iron-imidazole stretching frequencies and dissociation energies, and hyperfine spectral parameters for the ferric and ferrous, low-spin and high-spin configurations of the model heme. For both ferric and ferrous model hemes, the low-spin configuration is preferred by approximately 8 kcal/mol, which is consistent with experimental observations for bis-histidine hemes. We are now ready to begin Stage II. In Stage II of the project, we will model the electron transfer between the hemes of Ifc3, which will require converging the DFT density for heme clusters using their crystal structure geometries, followed by a calculation of the electron transfer matrix element, HIF (Marcus and Sutin, 1985). The magnitude of HIF between hemes will be used directly to define the electron transfer pathway in Ifc3. HIF can be calculated easily with the electron transfer module we recently added to the NWChem program. The ET module was built using new routines, as well as existing routines from NWChem's massively parallel electronic structure code, which has been optimized for good parallel performance. The amount of CPU time required for the calculation of HIF is the same as the time needed for the first iteration of an SCF calculation. The only input required are the names of the binary files containing the converged DFT Kohn-Sham orbitals corresponding to the electron transfer reactant and product states. The challenge of calculating HIF for the hemes in Ifc3 lies with the DFT calculation that precedes it. For our B3LYP geometry optimizations and property calculations, we used the Ahlrich VTZ basis set for iron and 6-311+G** for imidazole and porphyrin, a total of 906 spherical basis functions for each heme. For the heme quartets, we will use a smaller basis set (Ahlrich VTZ and 6-31G*), which contributes 591 functions to each heme, a total of 2364 basis functions for each heme quartet. We will perform single point DFT calculations for heme quartets from the Ifc3 crystal structure, and we will also include additional calculations that model the presence of the enzyme environment. Each DFT calculation will require at least 5000 node-hours, so we will require the maximum 75,000 node-hours of computation time on an IBM-SMP like Jupiter or ECS1 to complete such sophisticated calculations. This will enable us to calculate HIF for the hemes in Ifc3 and determine the influence of the protein environment on the electron transfer pathway.
Project Details
Project type
Exploratory Research
Start Date
2002-08-21
End Date
2003-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
Accompanying figures for the above publication.
Theoretical characterization of the electron transfer between the hemes of flavocytochrome c3 fumarate reductase (Ifc3)