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

• Narkhede, Y. B.; Bhardwaj, A.; Motsa, B. B.; Saxena, R.; Sharma, T.; Chapagain, P. P.; Stahelin, R. V. and Wiest, O. "Elucidating Residue-Level Determinants Affecting Dimerization of Ebola Virus Matrix Protein using High-Throughput Site Saturation Mutagenesis and Biophysical Approaches" 2023 Journal of Physical Chemistry B, 127 (29), pp.6449-6461. DOI: 10.1021/acs.jpcb.3c01759.
• Patel, H. N.; Haines, B. E.; Stauffacher, C. V.; Helquist, P. and Wiest, O. "Computational Study of Base-Catalyzed Thiohemiacetal Decomposition in Pseudomonas Mevalonii HMG-CoA Reductase" 2023 Journal of Physical Chemistry B, 127 (22), pp.4931-4938. DOI: 10.1021/acs.jpcb.2c08969.
• Maloney, M. P.; Coley, C. W.; Genheden, S.; Carson, N.; Helquist, P.; Norrby, P. O. and Wiest, O. "Negative Data in Data Sets for Machine Learning Training" 2023 Journal of Organic Chemistry, 88 (9), pp.5239-5241. DOI: 10.1021/acs.joc.3c00844.
• Saebi, M.; Nan, B. Z.; Herr, J. E.; Wahlers, J.; Guo, Z. C.; Zuranski, A. M.; Kogej, T.; Norrby, P. O.; Doyle, A. G.; Chawla, N. V. and Wiest, O. "On the use of Real-World Datasets for Reaction Yield Prediction" 2023 Chemical Science, 14 (19), pp.4997-5005. DOI: 10.1039/d2sc06041h.
• Zhu, Y. N.; Zhao, Y.; Wen, J. L.; Liu, S.; Huang, T. H.; Hatial, I.; Peng, X. X.; Al Janabi, H.; Huang, G.; Mittlesteadt, J.; Cheng, M.; Bhardwaj, A.; Ashfeld, B. L.; Kao, K. R.; Maeda, D. Y.; Dai, X.; Wiest, O.; Blagg, B.; Lu, X. M.; Cheng, L.; Wan, J. and Lu, X. "Targeting the Chromatin Effector Pygo2 Promotes Cytotoxic T Cell Responses and Overcomes Immunotherapy Resistance in Prostate Cancer" 2023 Science Immunology, 8 (81), eade4656. DOI: 10.1126/sciimmunol.ade4656.
• Wahlers, J.; Rosales, A. R.; Berkel, N.; Forbes, A.; Helquist, P.; Norrby, P. O. and Wiest, O. "A Quantum-Guided Molecular Mechanics Force Field for the Ferrocene Scaffold" 2022 Journal of Organic Chemistry, 87 (18), pp.12334-12341. DOI: 10.1021/acs.joc.2c01553.