Elizabeth A. Amin, Ph.D.
Assistant Professor

Office: 717 Delaware St SE, Room 417 Telephone Number: 612-626-2387 Fax Number: 612-626-6346 Email Address: eamin@umn.edu

Education:
B.A. 1996, M.S. 1997, Ph.D. 2002 University of Missouri-St. Louis
Tripos, Inc., 2002-2003

Research Interests:
My laboratory focuses on the design and optimization of metalloprotein-targeted chemical and biological warfare and anticancer therapeutics, incorporating computer-aided drug design, high-throughput screening and synthesis.  We are particularly interested in modeling and targeting the anthrax toxin lethal factor (LF), a Zn metalloprotease critical for anthrax pathogenesis. We apply a broad array of in silico techniques to systems of interest, from quantum-mechanical (QM) methods such as density functional and coupled-cluster theories to molecular dynamics (MD), molecular mechanics (MM), QM/MM, quantitative structure-activity relationship (QSAR) modeling, docking and scoring, pharmacophore mapping, and ADME/Tox prediction.  We also develop new software tools to model transition metals in unusual coordination states and/or charge environments, in order to facilitate the drug design process targeting large metal-bearing biomolecules.  We have recently begun collaborative work with the Department's Institute for Therapeutics Discovery and Development (ITDD) on the preparation and screening of pilot-scale compound libraries to be provided to the NIH Molecular Library Screening Center Network (MLSCN), to serve as biochemical and pharmacological tools for finding and exploring biological activities.

Current Projects:
Screening, design and optimization of druglike, nonpeptidic inhibitors of the anthrax toxin lethal factor (LF)

Novel descriptor-based modeling of zinc macromolecules including metalloenzymes, nanoparticles, and clusters; force field design; QM/MM methods; optimized multicoefficient correlation (MCCM) methods for Zn bio- and nanocenters

Prolyl-leucyl-glycinamide (PLG) modulation of dopamine receptors: mechanism elucidation and design of new therapeutics for Parkinson’s disease and schizophrenia (with the Johnson Group)

Chemically controlled assembly of bispecific antitumor antibody nanorings built from DHFR-DHFR fusion proteins and methotrexate linkers (with the Wagner Group)

Modeling the coordinative properties of highly fluorinated amines and hydrocarbons, toward the development of receptor-based chemical sensors with reduced biofouling (with the Bühlmann Group)

Publications:
Amin, E.A.; Truhlar, D.G;Zn coordination chemistry: development of benchmark suites for geometries, dipole moments and bond dissociation energies and their use to test and validate density functionals and molecular orbital theory,” J. Chem. Theory Comput. 2008, 4, 75-85

Settergren, N.; Bühlmann, P.; Amin, E.A. “Assessment of density functionals, semiempirical methods, and SCC-DFTB for protonated creatinine geometries,” in press

Amin, E.A. “Small-molecule databases for drug discovery and chemical space exploration,” in press

White, B.R.; Amin, E.A.; Wagner, C.R.; Truhlar, D.G. “Molecular modeling of geometries and charge distributions of small, drug-like molecules containing nitrogen heterocycles and exocyclic amino groups in the gas phase and aqueous solution,” in press

Hutt, O.E.; Chiu, T.-L.; Amin, E.A.; Reddy, B.S.; Nair, S.K.; Reiff, E.A.; Henri, J.T.; Greiner, J.F.; VanderVelde, D.; Himes, R.H.; Georg, G.I. “Total synthesis and evaluation of C24-benzyloxyepothilone C for tubulin assembly and cytotoxicity against MCF-7 breast cancer cells,” submitted

Settergren, N.; Bühlmann, P.; Amin, E.A. “Modeling a series of (perfluoro)trialkylamine solvent compounds,” in preparation

Wood, R.L.; Young-Dixon, B.; Gay, B.; Johnson, R.; Amin, E.A. “Evaluation of density functional theory, semiempirical molecular orbital theory, and molecular mechanics methods for prolyl-leucyl-glycinamide (PLG) analogues targeting the dopamine D2 receptor,” in preparation

Amin, E.A.; Welsh, W.J.  A preliminary in silico lead series of 2-phthalimidinoglutaric acid analogs designed as MMP-3 inhibitors.  J. Chem. Inf. Model. 2006, 46, 2104-2109