Molecular mechanical modeling of iron-sulfur metalloproteins I: Rubredoxins

INOR 274

David W. Mulder, Department of Chemistry and Biochemistry, Calvin College, Grand Rapids, MI 49546 and Robert K. Szilagyi, Szilagyi@Montana.EDU, Department of Chemistry and Biochemistry, Montana State University, Bozeman, MT 59717.
Iron-sulfur clusters play important roles in biology by participating in plant photosynthesis, nitrogen fixation, steroid metabolism, and oxidative phosphorylation processes. The aim of our work is to develop computational models employing molecular mechanical force field AMBER96 for studying the electronic and geometric structures of iron-sulfur metalloproteins and the related biomimetic synthons. As the first step of this work, we developed parameter sets for iron tetrathiolates in ferric and ferrous oxidation states as models for rubredoxin active sites. For parameter development, we used experimental structures from Cambridge Crystallographic Database and Protein Databank in addition to density functional theory calculations using Gaussian03. The molecular mechanical calculations and parameter optimization were performed in the molecular modeling software TINKER. The optimized parameters reproduced experimental structural data within 0.02 Å and 3° in bond lengths and angles, respectively. Our force field model allows for rapid structural modeling of rubredoxins at reasonable accuracy for docking simulations and electron-transfer pathway calculations, preliminary geometries for higher level electronic calculations and parameters for QM/MM integrated methods, and can aid the refinement of low resolution crystal structures.
 

Bioinorganic Modeling and Other Chemistry
7:00 PM-9:00 PM, Sunday, 13 March 2005 Convention Center -- Hall D, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, 14 March 2005 Convention Center -- Sails Pavilion, Sci-Mix

Division of Inorganic Chemistry

The 229th ACS National Meeting, in San Diego, CA, March 13-17, 2005