Biosciences Graduate Program

Michael Ashley Spies, PhD


Associate Professor of Biochemistry
Associate Professor of Medicinal & Natural Products Chemistry

Contact Information

Office: S313 PHAR
Iowa City, IA 52242
Phone: 319-353-5645

Web: M. Ashley Spies Laboratory
Web: College of Pharmacy Profile


BA, University of Kansas
MS, University of Kansas
PhD, University of Kansas

Fellowship, Osaka University, Institute for Scientific and Industrial Research
Post Doctorate, Dept of Chemistry, University of California, Davis

Education/Training Program Affiliations

Department of Biochemistry PhD

Research Summary

Our research group investigates the fundamental properties of protein-ligand interactions, from a physical and chemical perspective. Our primary focus is on pharmaceutically relevant enzymes. The application and development of computational chemistry often plays a central role in addressing research questions centering on the discovery and design of novel ligands to validated drug targets. Computational insights are bolstered by in vitro and in vivo assays. Ongoing projects include: i) development of parallelized in silico docking using high performance computing (HPC) on the University of Iowa's Helium cluster, ii) use of steered molecular dynamics to perform highly accurate and precise free energy calculations to accurately rank order drug leads to a number of antimicrobial and antineoplastic targets, iii) use of hybrid QM/MM electronic structure methods to understand remote allosteric modulation of enzyme catalytic power and iv) development of cheminformatics tools for parsing attractive regions of chemical space in screening libraries.

Selected Publications

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Marsden A, King J, Spies M, Kim O, Yahr T.  Inhibition of Pseudomonas aeruginosa ExsA DNA-Binding Activity by N-Hydroxybenzimidazoles..  Antimicrobial agents and chemotherapy.  2015 November 16. 60(2):766-76.

Dean S, Whalen K, Spies M,  .  Biosynthesis of a Novel Glutamate Racemase Containing a Site-Specific 7-Hydroxycoumarin Amino Acid: Enzyme–Ligand Promiscuity Revealed at the Atomistic Level.  ACS Cent. Sci..  2015 September. 

Subramanyam S, Jones W, Spies M, Spies M.  Contributions of the RAD51 N-terminal domain to BRCA2-RAD51 interaction .  Nucleic Acids Res.  2013 October. 41(19):9020-32.

Whalen K, Chau A, Spies M.  In silico Optimization of a Fragment-Based Hit Yields Biologically Active, High-Efficiency Inhibitors for Glutamate Racemase.  ChemMedChem.  2013 August. 

Spies M.  Nexus Between Protein–Ligand Affinity Rank-Ordering, Biophysical Approaches, and Drug Discovery.  ACS Med. Chem. Lett.  2013. 4(10):895-897.

Whalen K, Chang K, Spies M.  Hybrid Steered Molecular Dynamics-Docking: An Efficient Solution to the Problem of Ranking Inhibitor Affinities Against a Flexible Drug Target.  Molecular informatics.  2011 May. 30(5):459-471.

Whalen K, Tussey K, Blanke S, Spies M.  Nature of allosteric inhibition in glutamate racemase: discovery and characterization of a cryptic inhibitory pocket using atomistic MD simulations and pKa calculations.  The Journal of Physical Chemistry. B.  2011 April. 115(13):3416-24.

Whalen K, Pankow K, Blanke S, Spies M.  Exploiting Enzyme Plasticity in Virtual Screening: High Efficiency Inhibitors of Glutamate Racemase.  ACS medicinal chemistry letters.  2010 April. 1(1):13-Sep.

Spies M, Reese J, Dodd D, Pankow K, Blanke S, Baudry J.  Determinants of catalytic power and ligand binding in glutamate racemase.  Journal of the American Chemical Society.  2009 April. 131(14):5274-84.

Spies M, Toney M.  Intrinsic primary and secondary hydrogen kinetic isotope effects for alanine racemase from global analysis of progress curves.  Journal of the American Chemical Society.  2007 September. 129(35):10678-85.

Date Last Modified: 06/06/2016 - 13:17:48