Michael Ashley Spies

Associate Professor
Associate Professor of Biochemistry
Associate Professor of Pharmaceutical Science Experimental Therapeutics - Medicinal and Natural Products Chemistry

Contact Information

Primary Office
Medicinal & Natural Products Chemistry, 115 S Grand Av
Iowa City, IA 52242


Staff Contact

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.


Vance, N. R., Gakhar, L. & Spies, M. A. (2017). Allosteric Tuning of Caspase-7: A Fragment-Based Drug Discovery Approach. Angewandte Chemie (International ed. in English), 56(46), 14443-14447. PMID: 28940929.

Hengel, S. R., Malacaria, E., da Folly Silva Constantino, L., Bain, F. E., Diaz, A., Koch, B. G., Yu, L., Wu, M., Pichierri, P., Spies, M. A. & Spies, M. (2016). Small-molecule inhibitors identify the RAD52-ssDNA interaction as critical for recovery from replication stress and for survival of BRCA2 deficient cells. eLife, 5. PMID: 27434671.

Marsden, A. E., King, J. M., Spies, M. A., Kim, O. K. & Yahr, T. L. (2015). Inhibition of Pseudomonas aeruginosa ExsA DNA-Binding Activity by N-Hydroxybenzimidazoles. Antimicrobial agents and chemotherapy, 60(2), 766-76. PMID: 26574012.

Dean, S. F., Whalen, K. L. & Spies, M. A. (2015). Biosynthesis of a Novel Glutamate Racemase Containing a Site-Specific 7-Hydroxycoumarin Amino Acid: Enzyme-Ligand Promiscuity Revealed at the Atomistic Level. ACS central science, 1(7), 364-373. PMID: 26539562.

Spies, M. A. (2013). Nexus Between Protein–Ligand Affinity Rank-Ordering, Biophysical Approaches, and Drug Discovery. ACS Medicinal Chemistry Letters, 4(10), 895-897. DOI: 10.1021/ml4003502.

Subramanyam, S., Jones, W. T., Spies, M. & Spies, M. A. (2013). Contributions of the RAD51 N-terminal domain to BRCA2-RAD51 interaction. Nucleic acids research, 41(19), 9020-32. PMID: 23935068.

Whalen, K. L., Chau, A. C. & Spies, M. A. (2013). In silico optimization of a fragment-based hit yields biologically active, high-efficiency inhibitors for glutamate racemase. ChemMedChem, 8(10), 1681-9. PMID: 23929705.

Whalen, K. L., Spies, M. A. (2013). Flooding enzymes: quantifying the contributions of interstitial water and cavity shape to ligand binding using extended linear response free energy calculations. Journal of chemical information and modeling, 53(9), 2349-59. PMID: 24111836.

Whalen, K. L., Chang, K. & Spies, M. (2011). Hybrid Steered Molecular Dynamics-Docking: an efficient solution to the problem of ranking inhibitor affinities against a flexible drug target. Molecular Informatics, 30(5), 459-471.

Whalen, K. L., Pankow, K. L., Blanke, S. R. & Spies, M. (2011). Nature of Allosteric Inhibition in Glutamate Racemase: Discovery and Characterization of a Cryptic Inhibitory Pocket using Atomistic MD Simulations and pKa Calculations. J. Phys. Chem. B., 115(13), 3416-24.

Whalen, K. L., Pankow, K. L., Blanke, S. R. & Spies, M. (2010). Exploiting Enzyme Plasticity in Virtual Screening: High Efficiency Inhibitors of Glutamate Racemase. ACS Med. Chem. Lett., 1(1), 9-13.

Lin, L. J., Yoshinaga, A., Lin, Y., Guzman, C., Chen, Y. H., Mei, S., Lagunas, A. M., Koike, S., Iwai, S., Spies, M., Nair, S. K., Mackie, R. I., Ishino, Y. & Cann, I. K. (2010). Molecular analyses of an unusual translesion DNA polymerase from Methanosarcina acetivorans C2A. J. Mol. Biol., 397(1), 13-30.