Kasper Harpsøe

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• CV
• Research outputs
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I have worked within computational medicinal chemistry since I started my PhD in 2003 and have extensive experience with most molecular modeling techniques. Since 2014, I have been part of the Gloriam Group (gloriamgroup.org), which has G Protein-Coupled Receptors (GPCRs) as the main research focus. My role in the group is project manager for our activities within computatoional drug design of small molecule and peptide ligands. Most of our work are in multidisciplinary drug discovery projects in close collaboration with medicinal chemists, molecular pharmacologist, structural biologists and data scientists from both academia and industry. Our focus is mainly on biased signalling (fuctional selectivity) of GPCRs, design of inhibitors of protein-protein interactions in intracellular signalling and orthosteric GPCR ligands. In recent years, our focus has changed from traditional small molecule ligands to peptides. 

Additionally, we host the GPCRdb (gpcrdb.org), which contains reference data, interactive visualisation and experiment design tools for GPCRs. GPCRdb curates sequence alignments, structures and receptor mutations from literature and we provide, among other things, interactive diagrams that visualise receptor residues (e.g. snakeplot and helix box plot) and relationships (e.g phylogenetic trees).

Selected publications

1. Published

   Molecular insights into ligand recognition and G protein coupling of the neuromodulatory orphan receptor GPR139

   Zhou, Y., Daver, H., Trapkov, B., Wu, L., Wu, M., Harpsøe, Kasper, Gentry, Patrick Ryan, Liu, K., Larionova, M., Liu, J., Chen, N., Bräuner-Osborne, Hans, Gloriam, David E., Hua, T. & Liu, Z. J., 2022, In: Cell Research. 32, 2, p. 210-213

   Research output: Contribution to journal › Letter › Research › peer-review

2. Published

   Ligand-directed bias of G protein signaling at the dopamine D₂ receptor

   Moo, Ee Von, Harpsøe, Kasper, Hauser, Alexander Sebastian, Masuho, I., Bräuner-Osborne, Hans, Gloriam, David E. & Martemyanov, K. A., 2022, In: Cell Chemical Biology. 29, 2, p. 226-238

   Research output: Contribution to journal › Journal article › Research › peer-review

3. Published

   Molecular Determinants underlying Delta Selective Compound 2 (DS2) Activity at δ-Containing GABAA Receptors

   Falk-Petersen, C. B., Rostrup, Frederik, Löffler, R., Buchleihtner, S., Harpsøe, Kasper, Gloriam, David E., Frølund, Bente & Wellendorph, Petrine, 2021, In: Molecular Pharmacology. 100, 1, p. 46-56

   Research output: Contribution to journal › Journal article › Research › peer-review

4. Published

   Structural insights into the lipid and ligand regulation of serotonin receptors

   Xu, P., Huang, S., Zhang, H., Mao, C., Zhou, X. E., Cheng, X., Simon, Icaro Ariel, Shen, D., Yen, H., Robinson, C. V., Harpsøe, Kasper, Svensson, B., Guo, J., Jiang, H., Gloriam, David E., Melcher, K., Jiang, Y., Zhang, Y. & Xu, H. E., 2021, In: Nature. 592, p. 469-473

   Research output: Contribution to journal › Journal article › Research › peer-review

5. Published

   Delineation of molecular determinants for FR900359 inhibition of G_q/11 unlocks inhibition of Gα_s

   Boesgaard, M. W., Harpsøe, Kasper, Malmberg, M., Underwood, C. R., Inoue, A., Mathiesen, Jesper M., König, G. M., Kostenis, E., Gloriam, David E. & Bräuner-Osborne, Hans, 2020, In: Journal of Biological Chemistry. 295, 40, p. 13850-13861

   Research output: Contribution to journal › Journal article › Research › peer-review

6. Published

   5-HT2C Receptor Structures Reveal the Structural Basis of GPCR Polypharmacology

   Peng, Y., McCorvy, J. D., Harpsøe, Kasper, Lansu, K., Yuan, S., Popov, P., Qu, L., Pu, M., Che, T., Nikolajsen, L. F., Huang, X., Wu, Y., Shen, L., Bjørn-Yoshimoto, Walden, Ding, K., Wacker, D., Han, G. W., Cheng, J., Katritch, V., Jensen, Anders A., Hanson, M. A., Zhao, S., Gloriam, David E., Roth, B. L., Stevens, R. C. & Liu, Z., 2018, In: Cell. 172, 4, p. 719-730 P719-730.E14.

   Research output: Contribution to journal › Journal article › Research › peer-review

7. Published

   Total synthesis and structure–activity relationship studies of a series of selective G protein inhibitors

   Xiong, X., Zhang, H., Underwood, C. R., Harpsøe, Kasper, Gardella, T. J., Wöldike, M. F., Mannstadt, M., Gloriam, David E., Bräuner-Osborne, Hans & Strømgaard, Kristian, 2016, In: Nature Chemistry. 8, 11, p. 1035-1041 7 p.

   Research output: Contribution to journal › Journal article › Research › peer-review

8. Published

   Rational design of a heterotrimeric G protein α subunit with artificial inhibitor sensitivity

   Malfacini, D., Patt, J., Annala, S., Harpsøe, Kasper, Eryilmaz, F., Reher, R., Crüsemann, M., Hanke, W., Zhang, H., Tietze, D., Gloriam, David E., Bräuner-Osborne, Hans, Strømgaard, Kristian, König, G. M., Inoue, A., Gomeza, J. & Kostenis, E., 12 Apr 2019, In: The Journal of Biological Chemistry. 294, 15, p. 5747-5758

   Research output: Contribution to journal › Journal article › Research › peer-review

9. Published

   Unraveling the high- and low-sensitivity agonist responses of nicotinic acetylcholine receptors

   Harpsøe, Kasper, Ahring, P. K., Christensen, J. K., Jensen, M. L., Peters, D. & Balle, T., 27 Jul 2011, In: Journal of Neuroscience. 31, 30, p. 10759-10766

   Research output: Contribution to journal › Journal article › Research › peer-review