The overall goal of the Kersten lab is the elucidation of the molecular recognition between small drug-like molecules and their biological targets. This does not only account for binding affinity (does it bind and if so, how tight?), but also thermodynamics (what is the binding energy?) and kinetics (how fast does it bind and unbind?). Our toolbox to study molecular interactions covers both theoretical and experimental methods. And of course, we also apply our methods for ligand identification and optimization in several MedChem projects.
Key techniques: Computer-aided, structure based ligand design by molecular docking and molecular dynamic simulations (MD) as well as experimental binding assays like microscale thermophoresis (MST) or isothermal titration calorimetry (ITC).
Research system: We keep it "simple" – only in silico and in vitro. Besides several protein model systems, we are highly interested in the interactions between RNA and small molecules.
- Kersten, C.; Clower, S.; Barthels, F. Hic Sunt Dracones: Molecular Docking in Uncharted Territories with Structures from AlphaFold2 and RoseTTAfold. J. Chem. Inf. Model. 2022, 63 (7), 2218–2225. https://doi.org/10.1021/acs.jcim.2c01400.
- Hammerschmidt, S. J.; Huber, S.; Braun, N. J.; Lander, M.; Steinmetzer, T.; Kersten, C. Thermodynamic Characterization of a Macrocyclic Zika Virus NS2B/NS3 Protease Inhibitor and Its Acyclic Analogs. Arch. Pharm. (Weinheim). 2022, No. November. https://doi.org/10.1002/ardp.202200518.
- Kallert, E.; Fischer, T. R.; Schneider, S.; Grimm, M.; Helm, M.; Kersten, C. Protein-Based Virtual Screening Tools Applied for RNA-Ligand Docking Identify New Binders of the PreQ1-Riboswitch. J. Chem. Inf. Model. 2022, 62 (17), 4134–4148. https://doi.org/10.1021/acs.jcim.2c00751.
- Wettstein, L.; Knaff, P. M.; Kersten, C.; Müller, P.; Weil, T.; Conzelmann, C.; Müller, J. A.; Brückner, M.; Hoffmann, M.; Pöhlmann, S.; Schirmeister, T.; Landfester, K.; Münch, J.; Mailänder, V. Peptidomimetic Inhibitors of TMPRSS2 Block SARS-CoV-2 Infection in Cell Culture. Commun. Biol. 2022, 5 (1), 681. https://doi.org/10.1038/s42003-022-03613-4.
- Kersten, C.; Fleischer, E.; Kehrein, J.; Borek, C.; Jaenicke, E.; Sotriffer, C.; Brenk, R. How to Design Selective Ligands for Highly Conserved Binding Sites: A Case Study Using N-Myristoyltransferases as a Model System. J. Med. Chem. 2020, 63 (5), 2095–2113. https://doi.org/10.1021/acs.jmedchem.9b00586.