Olaf Wiest

Research Interests

The central topic of the research in the Wiest group is how molecules interact and react. The structure and energetics of non-covalent complexes and transition states is probed theoretically and experimentally. The detailed understanding of intermolecular interactions can then be exploited for the design of assays for biophysical studies and for drug design. Four distinct areas of research are currently under investigation: (1) development of epigenetic modulators targeting histone deacetylases and bromodomains as chemical tools and drug leads, (2) rare and neglected diseases, specifically Niemann Pick Type C disease, (3) mechanistic studies of transition metal and enzyme catalyzed reactions, and (4) development of Q2MM methods for the virtual screening of chiral ligands for asymmetric catalysis.

The research in the Wiest group uses a wide range of experimental and computational methods that are applied to fundamental and applied problems in organic and biophysical chemistry. In this work, we collaborate with a number of other researchers in synthetic chemistry, biology, physics, and at medical schools at Notre Dame and around the world.

Selected Publications

• Bennin, E.; O'Connell, R. J.; Zavala, C.; González-Montiel, G. A.; Wiest, O. and Darko, A. "Strategic Ligand Design for Modulating Axial Sites in Dirhodium Catalysts: Towards Enhanced Asymmetric Cyclopropanation" 2026 Dalton Transactions, 55 (33), pp.12313–12319. DOI: 10.1039/d6dt01202g.
• Chawla, N. V.; Gonzalez-Montiel, G. A.; Guo, K. H.; Guo, T. C.; Hua, T.; Huang, X. B.; Inae, E.; Jiang, M.; Le, K.; Liu, G.; Maier, J. C.; Moniz, N.; Nogueira, B.; Pan, D.; Piguave, B. V.; Savoie, B. M.; Schofield, A. B.; Shen, Y. L.; Taylor, A.; Zhang, X. L.; Zhu, Y. H. and Wiest, O. "Organic Chemistry as a Catalyst for AI Innovation: Challenges, Methods, and Emerging Paradigms" 2026 Chemical Reviews, 126 (13), pp.7587–7635. DOI: 10.1021/acs.chemrev.5c01081.
• Yu, X. T.; Gonzalez-Montiel, G. A.; Shit, P.; Chang, M. Y.; Wiest, O. and Mobashery, S. "A Lactone-Enabled Approach to Metronidazole-Based Scaffolds" 2026 Journal of Organic Chemistry, 91 (22), pp.7590–7595. DOI: 10.1021/acs.joc.6c00559.
• Farrugia, M.; Helquist, P.; Norrby, P. O. and Wiest, O. "Rapid FF Generation Via Hessian-Informed Initial Parameters and Automated Refinement" 2026 Journal of Chemical Theory and Computation, 22 (1), pp.469–476. DOI: 10.1021/acs.jctc.5c01751.
• Stenfors, B. A.; Cadge, J. A.; Aikonen, S.; Luchini, G.; Wahlers, J.; Koh, K.; Muuronen, M.; Menche, M.; Pfeifle, M.; Keto, A.; Paton, R. S.; Sigman, M. S. and Wiest, O. "Conformation Dependent Features of Bisphosphine Ligands" 2025 Journal of Organic Chemistry, 90 (39), pp.13874–13884. DOI: 10.1021/acs.joc.5c01682.
• Motsa, B. B.; Bhowal, B.; Narkhede, Y. B.; Karki, U.; Ramirez, V. T.; Eger, S. W.; Wiest, O.; Chapagain, P. P. and Stahelin, R. V. "Variants of the Ebola Virus Matrix Protein VP40 have Differential Effects on Oligomerization and Plasma Membrane Interactions" 2025 Journal of Biological Chemistry, 301 (9), 110489. DOI: 10.1016/j.jbc.2025.110489.