Dr. Benjamin Gherman

B. S. Chemistry (with Computational Chemistry option), Carnegie Mellon University (May 1998)

B. S. Mathematics, Carnegie Mellon University (May 1998)

M. A. Chemistry, Columbia University (October 1999) 

M. Phil. Chemistry, Columbia University (February 2002) 

Ph. D. Chemistry, Columbia University (October 2003)

http://www.csus.edu/indiv/g/ghermanb/

Chem. 1A, Chem. 140A & B, Chem. 142, & Chem. 245

Computational Modeling of Bioinorganic Chemistry

From Biomimetic Models to Active-Site Models to the Metalloenzyme

The principal goal of my research involves the application of computational chemistry methods to study the catalytic chemistry of metalloenzymes and related biomimetic systems.   Pertinent methodologies will also be examined and be subject to optimization.  At present, two major projects are proposed: (1) dependence of the catalytic activity of peptide deformylase and biomimetic models thereof on the identity of the metal center; and (2) metal-binding specificity in and metal transfer from copper chaperone proteins.
 
(1) Peptide deformylase (PDF) catalyzes the hydrolytic cleavage of the formyl group at the N-terminus of nascent eubacterial proteins during protein synthesis.  As PDF is essential for bacterial survival but absent in higher animals, PDF constitutes a promising target for a new class of antibacterial agents, making investigation of the structure and function of this enzyme an important endeavor.  PDF is also of great interest from the bioinorganic viewpoint, as it is the only example of an iron metalloamidase.  The choice of iron by nature is intriguing considering the inherent instability of FeII towards oxidation and that PDF catalyzes a non-redox-active reaction.  Research here will focus on (a) how enzyme activity and catalytic mechanism vary when different metals (e.g., FeII, ZnII, NiII) are present at the PDF active site, (b) how electronic changes at the active site affect the deformylation reaction, and (c) how the hydrogen bonding environment of the protein active site affects the deformylation reaction.

 (2) Copper ions serve as essential co-factors for metalloproteins (e.g. for those involved in energy generation and iron uptake and distribution), but at the same time are potentially toxic to living cells due to their ability to bind with high affinity to partially folded proteins, their high redox activity, and their propensity to catalyze the auto-oxidation of lipids, proteins, and nucleic acids.  Copper chaperone proteins have consequently evolved as part of a complex network for the intracellular trafficking of copper and help to control the amount of free intracellular copper.  Maintenance of intracellular copper ion concentrations by these chaperone proteins is not presently well understood and constitutes an important problem in bioinorganic chemistry.  My research will examine the origin of these chaperone proteins’ specificity for copper and the mechanism for copper transfer between these proteins.

Collaborative research projects are also being carried out with Prof. James Miranda in the area of metal-salen electrochemistry and with Prof. John Spence in the area of photoreactivity of enediynes.

1. California State University, Sacramento research and creativity award, 2008 & 2009.

2. Wiley-International Journal of Quantum Chemistry Young Investigator Award, 2008.

3. Developmental project allocation (title: “Using Mixed Quantum Mechanics/Molecular Mechanics Calculations to Assess the Effects of Mutations on the Catalytic Activity of Peptide Deformylase”) of 24,000 service units from the National Center for Supercomputing Applications (NCSA), 2007-2008

1. B. F. Gherman and C. J. Cramer.  “Quantum Chemical Studies of Molecules Incorporating a Cu2O22+ Core.”  Coord. Chem. Rev., 253, 723-753 (2009).

2. A. H. Winter, D. E. Falvey, C. J. Cramer, B. F. Gherman.  “Benzylic Cations with Triplet Ground States: Computational Studies of Aryl Carbenium Ions, Silylenium Ions, Nitrenium Ions and Oxenium Ions Substituted with meta Pi Donors.”  J. Am. Chem. Soc., 129, 10113-10119 (2007).

3. L. R. M. Hill, B. F. Gherman, N. W. Aboelella, C. J. Cramer, W. B. Tolman.  “Electronic Tuning of b-Diketiminate Ligands with Fluorinated Substituents: Effects on the O2-Reactivity of Mononuclear Cu(I) Complexes.”  Dalton Trans. 4944-4953 (2006).

4. D. E. Heppner, B. F. Gherman, W. B. Tolman, C. J. Cramer.  “Can an Ancillary Ligand Lead to a Thermodynamically Stable End-on 1:1 Cu-O2 Adduct Supported by a β-Diketiminate Ligand?”  Dalton Trans. 4773-4782 (2006).

5. B. F. Gherman, W. B. Tolman, C. J. Cramer.  “Characterization of the Structure and Reactivity of Monocopper-Oxygen Complexes Supported by β-Diketiminate and Anilido-Imine Ligands.”  J. Comput. Chem. 27, 1950-1961 (2006).

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