Spies, Michael Ashley - University of Iowa - Department of Biochemistry

研究领域

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.

近期论文

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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. DOI: 10.7554/eLife.14740. 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. DOI: 10.1021/acscentsci.5b00211. 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. DOI: 10.1128/AAC.02242-15. 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. DOI: 10.1093/nar/gkt691. 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. DOI: 10.1002/cmdc.201300271. 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. DOI: 10.1021/ci400244x.