Kasper Harpsøe

Kasper Harpsøe

Senior Advisor

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

    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 journalJournal articleResearchpeer-review

  2. 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 journalJournal articleResearchpeer-review

  3. E-pub ahead of print

    Delineation of molecular determinants for FR900359 inhibition of Gq/11 unlocks inhibition of Gαs

    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, 4 Aug 2020, In : The Journal of Biological Chemistry.

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. 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 journalJournal articleResearchpeer-review

  5. Published

    GPCRdb in 2018: adding GPCR structure models and ligands

    Pándy-Szekeres, G., Munk, Christian, Tsonkov, T. M., Mordalski, Stefan Mateusz, Harpsøe, Kasper, Hauser, Alexander Sebastian, Bojarski, A. J. & Gloriam, David E., 2018, In : Nucleic Acids Research. 46, D1, 7 p., gkx1109.

    Research output: Contribution to journalJournal articleResearchpeer-review

  6. Published

    Structural insight to mutation effects uncover a common allosteric site in class C GPCRs

    Harpsøe, Kasper, Boesgaard, M. W., Munk, Christian, Bräuner-Osborne, Hans & Gloriam, David E., 2017, In : Bioinformatics (Oxford, England). 33, 8, p. 1116-1120 5 p., btw784.

    Research output: Contribution to journalJournal articleResearchpeer-review

  7. Published

    GPCRdb: an information system for G protein-coupled receptors

    Isberg, V., Mordalski, S., Munk, Christian, Rataj, K., Harpsøe, Kasper, Hauser, Alexander Sebastian, Vroling, B., Bojarski, A. J., Vriend, G. & Gloriam, David E., 4 Jan 2016, In : Nucleic Acids Research. 44, D1, p. D356-64

    Research output: Contribution to journalJournal articleResearchpeer-review

  8. 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 journalJournal articleResearchpeer-review

ID: 1428429