Theoretical Medicinal Chemistry

Prof Dr. Marcel Bermúdez

• Computerunterstütztes Wirkstoffdesign
• In silico Pharmakologie
• Dynamische Pharmakophormodelle
• Virtuelles Screening
• G-Protein-gekoppelte Rezeptoren
• Strukturelle Pharmakogenomik

Academic Education

02.2011 – 06.2015

Promotion, Freie Universität Berlin, Institut für Pharmazie, Abschluss: Dr. rer. nat. (summa cum laude)

since 11.2010

Approbation als Apotheker

10.2004 – 2009

Studium der Pharmazie, TU Braunschweig

Positions

since 10.2021

Universitätsprofessor (W1) für Theoretische Medizinische Chemie, Universität Münster, Institut für Pharmazeutische und Medizinische Chemie

03.2019 – 2021

Nachwuchsgruppenleiter (DFG - Eigene Stelle), Freie Universität Berlin, Institut für Pharmazie

07.2015 – 2019

Postdoc, Freie Universität Berlin, Institut für Pharmazie

09.2017 – 2017

Visiting Postdoc, University of Cambridge (UK), Centre for Molecular Informatics, Department of Chemistry

09.2016 – 2016

Visiting Postdoc, The Hebrew University of Jerusalem (Israel), Robert H. Smith Faculty of Agriculture, Food and Environment

External Functions

since 10.2023

DPhG-Regionalgruppe Westfalen-Lippe (Vorsitzender)

since 09.2023

Verband der Pharmazieprofessoren an Pharmazeutischen Hochschulen e.V. (Mitglied)

since 10.2021

Center for Multiscale Theory and Computation (CMTC) (Mitglied)

since 01.2012

Deutsche Pharmazeutische Gesellschaft (DPhG) (Mitglied)

• Dynamic pharmacophores for the discovery of specific modulators of G protein-coupled receptors. (2022 – 2023)
  Individual Granted Project: DFG - Sachbeihilfe/Einzelförderung | Project Number: BE 6702/1-1

• Wunsch, F., Nguyen, TN., Wolber, G. and Bermudez, M., “Structural determinants of sphingosine-1-phosphate receptor selectivity.” ArchPharm 356, 12 (2023): Article 2300387. doi: 10.1002/ardp.202300387.
• Di Pizio, A., Bermudez, M., De Graaf, C. and Jockers, R., “Peptide-binding GPCRs coming of age.” Front Endocrinol (Lausanne) 14 (2023): Article 1189508. doi: 10.3389/fendo.2023.1189508.
• Heinz, C., Bermudez, M., Jaiswal, N., Große, C., Kauk, M., Hoffmann, C. and Holzgrabe, U., “Hybridization into a Bitopic Ligand Increased Muscarinic Receptor Activation for Isopilocarpine but Not for Pilocarpine Derivatives.” Journal of Natural Products 86, 4 (2023): 869–881. doi: 10.1021/acs.jnatprod.2c01079.
• Kolb, P., Kenakin, T., Alexander, S., Bermudez, M., Bohn, L., Breinholt, C, Bouvier, M., Hill, S., Kostenis, E., Martemyanov, K., Neubig, R., Onaran, O., Rajagopal, S., Roth, B., Selent, J., Shukla, A., Sommer, M. and D, Gloriam, “Community guidelines for GPCR ligand bias: IUPHAR review 32.” British Journal of Pharmacology 179, 14 (2022): 3651–3674. doi: 10.1111/bph.15811.
• Denzinger, K., Nguyen, TN., Noonan, T., Wolber, G. and Bermudez, M., “Biased Ligands Differentially Shape the Conformation of the Extracellular Loop Region in 5-HT2B Receptors.” Int J Mol Sci 21 (2020): 9728–9728. doi: 10.3390/ijms21249728.
• Dumitrascuta, M., Bermudez, M., Trovato, O., Neve, JD., Ballet, S., Wolber, G. and Spetea, M., “Antinociceptive Efficacy of the µ-Opioid/Nociceptin Peptide-Based Hybrid KGNOP1 in Inflammatory Pain without Rewarding Effects in Mice: An Experimental Assessment and Molecular Docking.” Molecules 26 (2021): 3267–3267. doi: 10.3390/molecules26113267.
• Bock, A. and Bermudez, M., “Allosteric coupling and biased agonism in G protein‐coupled receptors.” FEBS J 288 (2021): 2513–2528. doi: 10.1111/febs.15783.
• Agnetta, L., Bermudez, M., Riefolo, F., Matera, C., Claro, E., Messerer, R., Littmann, T., Wolber, G., Holzgrabe, U. and Decker, M., “Fluorination of Photoswitchable Muscarinic Agonists Tunes Receptor Pharmacology and Photochromic Properties.” J Med Chem 62 (2019): 3009–3020. doi: 10.1021/acs.jmedchem.8b01822.
• Kalash, L., Winfield, I., Safitri, D., Bermudez, M., Carvalho, S., Glen, R., Ladds, G. and Bender, A., “Structure‐based identification of dual ligands at the A2AR and PDE10A with anti‐proliferative effects in lung cancer cell‐lines.” Journal of Cheminformatics 13, 1 (2021): Article 17 (2021). doi: 10.1186/s13321-021-00492-5.
• Volpato, D., Kauk, M., Messerer, R., Bermudez, M., Wolber, G., Bock, A., Hoffmann, C. and Holzgrabe, U., “The Role of Orthosteric Building Blocks of Bitopic Ligands for Muscarinic M1 Receptors.” ACS Omega 5 (2020): 31706–31715. doi: 10.1021/acsomega.0c04220.
• Holze, J., Bermudez, M., Pfeil, EM., Kauk, M., Bödefeld, T., Irmen, M., Matera, C., Dallanoce, C., Amici, MD., Holzgrabe, U., König, GM., Tränkle, C., Wolber, G., Schrage, R., Mohr, K., Hoffmann, C., Kostenis, E. and Bock, A., “Ligand-Specific Allosteric Coupling Controls G-Protein-Coupled Receptor Signaling.” ACS Pharmacology & Translational Science 3, 5 (2020): 859–867. doi: 10.1021/acsptsci.0c00069.
• Schaller, D., Šribar, D., Noonan, T., Deng, L., Nguyen, TN., Pach, S., Machalz, D., Bermudez, M. and Wolber, G., “Next generation 3D pharmacophore modeling.” WIREs 10, 4 (2020): Article e1468. doi: 10.1002/wcms.1468.
• Bermudez, M., Grabowski, M., Murgueitio, MS., Tiemann, M., Varga, P., Rudolf, T., Wolber, G., Weindl, G. and Rademann, J., “Biological Characterization, Mechanistic Investigation and Structure‐Activity Relationships of Chemically Stable TLR2 Antagonists.” ChemMedChem 15 (2020): 1364–1371. doi: 10.1002/cmdc.202000060.
• Dumitrascuta, M., Bermudez, M., Ballet, S., Wolber, G. and Spetea, M., “Mechanistic Understanding of Peptide Analogues, DALDA, [Dmt1]DALDA, and KGOP01, Binding to the Mu Opioid Receptor.” Molecules 25 (2020): Article 2087. doi: 10.3390/molecules25092087.
• Bermudez, M., “Novel BQCA‐ and TBPB‐Derived M1-Receptor Hybrid Ligands: Orthosteric Carbachol Differentially Regulates Partial Agonism.” ChemMedChem 14, 14 (2019): 1349–1358. doi: 10.1002/cmdc.201900283.
• Bermudez, M. and Bock, A., “Does Divergent Binding Pocket Closure Drive Ligand Bias for Class A GPCRs?.” Trends in Pharmacological Sciences 40, 4 (2019): 236–239. doi: 10.1016/j.tips.2019.02.005.
• Šribar, D., Grabowski, M., Murgueitio, MS., Bermudez, M., Weindl, G. and Wolber, G., “Identification and characterization of a novel chemotype for human TLR8 inhibitors.” European Journal of Medicinal Chemistry 179 (2019): 744–752. doi: 10.1016/j.ejmech.2019.06.084.
• Bermudez, M., Nguyen, TN., Omieczynski, C. and Wolber, G., “Strategies for the discovery of biased GPCR ligands.” Drug Discovery Today 24 (2019): 1031–1037. doi: 10.1016/j.drudis.2019.02.010.
• Bermudez, M., Bock, A., Krebs, F., Holzgrabe, U., Mohr, K., Lohse, MJ. and Wolber, G., “Ligand-Specific Restriction of Extracellular Conformational Dynamics Constrains Signaling of the M2 Muscarinic Receptor.” ACS Chem Biol 12 (2017): 1743–1748. doi: 10.1021/acschembio.7b00275.
• Bock, Andreas and Bermudez, Marcel, “A panoramic view on GPCRs: the 1st Berlin Symposium for Interdisciplinary GPCR research.” Naunyn-Schmiedeberg's Archives of Pharmacology 391 (2018): 769–771. doi: 10.1007/s00210-018-1513-5.
• Grabowski, Maria, Murgueitio, Manuela S., Bermudez, Marcel, Rademann, Jörg, Wolber, Gerhard and Weindl, Günther, “Identification of a pyrogallol derivative as a potent and selective human TLR2 antagonist by structure-based virtual screening.” Biochemical Pharmacology 154 (2018): 148–160. doi: 10.1016/j.bcp.2018.04.018.
• Schaller, David, Hagenow, Stefanie, Alpert, Gina, Naß, Alexandra, Schulz, Robert, Bermudez, Marcel, Stark, Holger and Wolber, Gerhard, “Systematic Data Mining Reveals Synergistic H3R/MCHR1 Ligands.” ACS Med Chem Lett 8, 6 (2017): 648–653. doi: 10.1021/acsmedchemlett.7b00118.
• Mortier, J., Prévost, J., Sydow, D., Teuchert, S., Omieczynski, C., Bermudez, M., R, Frédérick and Wolber, G., “Arginase Structure and Inhibition: Catalytic Site Plasticity Reveals New Modulation Possibilities.” Sci. Rep. 7 (2017): Article 13616. doi: 10.1038/s41598-017-13366-4.
• Tkachenko, A., Bermudez, M., Irmer-Stooff, S., Genkinger, D., Henkler-Stephani, F., Wolber, G. and Luch, A., “Nuclear transport of the human aryl hydrocarbon receptor and subsequent gene induction relies on its residue histidine 291.” Arch. Toxicol. 92 (2017): 1150–1160. doi: 10.1007/s00204-017-2129-0.
• Koehling, S., Kuenze, G., Lemmnitzer, K., Bermudez, M., Wolber, G., Schiller, J., Huster, D. and Rademann, J., “Chemoenzymatic Synthesis of Nonasulfated Tetrahyaluronan with a Paramagnetic Tag for Studying Its Complex with Interleukin-10.” Chem. Eur. J. 22 (2016): 5563–5574. doi: 10.1002/chem.201504459.
• Bock, A., Bermudez, M., Krebs, F., Matera, C., Chirinda, B., Sydow, D., Dallanoce, C., Holzgrabe, U., De, Amici M., Lohse, M., Wolber, G. and Mohr, K., “Ligand binding ensembles determine graded agonist efficacies at a G protein-coupled receptor.” J Biol Chem 291 (2016): 16375–16389. doi: 10.1074/jbc.M116.735431.
• Bermudez, M., Mortier, J., Rakers, C., Sydow, D. and Wolber, G., “More than a look into a crystal ball: protein structure elucidation guided by molecular dynamics simulations.” Drug Discovery Today 21 (2016): 1799–1805. doi: 10.1016/j.drudis.2016.07.001.
• Guerrieri, E., Bermudez, M., Wolber, G., Berzetei-Gurske, IP., Schmidhammer, H. and Spetea, M., “Structural determinants of diphenethylamines for interaction with the κ opioid receptor: Synthesis, pharmacology and molecular modeling studies.” Bioorganic and Medicinal Chemistry Letters 26, 19 (2016): 4769–4774. doi: 10.1016/j.bmcl.2016.08.031.
• Rakers, C., Bermudez, M., Keller, BG., Mortier, J. and Wolber, G., “Computational close up on protein-protein interactions: how to unravel the invisible using molecular dynamics simulations?.” WIREs 5 (2015): 345–359. doi: 10.1002/wcms.1222.
• Bermudez, M., Rakers, C. and Wolber, G., “Structural Characteristics of the Allosteric Binding Site Represent a Key to Subtype Selective Modulators of Muscarinic Acetylcholine Receptors.” Molecular Informatics 34 (2015): 526–530. doi: 10.1002/minf.201500025.
• Bermudez, M. and Wolber, G., “Structure versus function-The impact of computational methods on the discovery of specific GPCR-ligands.” Bioorganic & Medicinal Chemistry 23 (2015): 3907–3912. doi: 10.1016/j.bmc.2015.03.026.
• Mortier, J., Rakers, C., Bermudez, M., Murgueitio, MS., Riniker, S. and Wolber, G., “The impact of molecular dynamics on drug design: applications for the characterization of ligand-macromolecule complexes.” Drug Discovery Today 20 (2015): 686–702. doi: 10.1016/j.drudis.2015.01.003.
• Schmitz, J., van, der Mey D, Bermudez, M., Kloeckner, J., Schrage, R., Kostenis, E., Traenkle, C., Wolber, G., Mohr, K. and Holzgrabe, U., “Dualsteric Muscarinic Antagonists-Orthosteric Binding Pose Controls Allosteric Subtype Selectivity.” J Med Chem 57 (2014): 6739–6750. doi: 10.1021/jm500790x.
• Leschner, J., Wennerberg, G., Feierler, J., Bermudez, M., Welte, B., Kalatskaya, I., Wolber, G. and Faussner, A., “Interruption of the Ionic Lock in the Bradykinin B-2 Receptor Results in Constitutive Internalization and Turns Several Antagonists into Strong Agonists.” Journal of Pharmacology and Experimental Therapeutics 344 (2013): 85–95. doi: 10.1124/jpet.112.199190.
• Levay, M., Krobert, KA., Wittig, K., Voigt, N., Bermudez, M., Wolber, G., Dobrev, D., Levy, FO. and Wieland, T., “NSC23766, a Widely Used Inhibitor of Rac1 Activation, Additionally Acts as a Competitive Antagonist at Muscarinic Acetylcholine Receptors.” Journal of Pharmacology and Experimental Therapeutics 347 (2013): 69–79. doi: 10.1124/jpet.113.207266.
• Faussner, A., Schuessler, S., Feierler, J., Bermudez, M., Pfeifer, J., Schnatbaum, K., Tradler, T., Jochum, M., Wolber, G. and Gibson, C., “Binding characteristics of [3H]-JSM10292: a new cell membrane-permeant non-peptide bradykinin B2 receptor antagonist.” British Journal of Pharmacology 167 (2012): 839–853. doi: 10.1111/j.1476-5381.2012.02054.x.