Hugo Gutiérrez de Terán Castañón is a Senior Scientist at the CSIC, affiliated with the Center for Research in Nanomaterials and Nanotechnology (CINN), and Professor of Computational Biochemistry at Uppsala University. He holds a degree in Pharmacy from the University of Santiago de Compostela (USC, 1999), and a PhD in Experimental Sciences (specializing in Molecular Modeling and Computer-Aided Drug Design) from the Pompeu Fabra University of Barcelona (UPF, 2004). After an initial postdoctoral period at Uppsala University, where he focused on the development of computational methods for the affinity prediction of biological molecules within the framework of a multidisciplinary drug development project against malaria, in 2007 he created his own research group through the Parga Pondal Program for HR recruitment of the Xunta de Galicia, within the Galician Public Foundation for Genomic Medicine, directed by Dr. Ángel Carracedo. Thus began his current line of research on the study of the mechanism and regulation of G protein-coupled receptors (GPCRs), the family of membrane receptors targeted by 30% of the drugs on the market. When the first structures of these receptors became accessible, he completed a sabbatical at the Scripps Research Institute in California with Professor Raymond C. Stevens, one of the international reference laboratories in this field, where he conducted pioneering studies on the mechanisms of allosteric modulation of GPCRs. In 2012, a critical time of disinvestment in R&D&I in Spain, he received an offer to return to Uppsala, where he integrated his line of work into the computational biology program directed by Professor Johan Åqvist, first qualifying as a university lecturer (2015), then promoting to Full Professor (2021) and then Professor of Computational Biochemistry (2024) at that university. In November 2024, she returned to her native Asturias to establish the Computational Biochemistry and Structural Bioinformatics Laboratory at ISPA. She combines her extensive research career, with more than 100 scientific articles in high-impact journals (H index greater than 35), several funded projects, and almost a dozen doctoral theses, with the teaching she continues to provide at Uppsala University, her commitment to scientific outreach, and the transfer of knowledge and technology, as demonstrated by the creation of a company in the field of computer-assisted drug development.
Laboratory N-1, F-12A
ISPA-FINBA Building
Avda. Hospital Universitario s/n
33011 Oviedo
Telephone: +34 984016780
Email: h.g.teran@cinn.es
LinkedIn: Hugo Gutiérrez de Terán
BlueSky: @hugogdtc.bsky.social
| Name | Institution | Euraxess Classification |
|---|---|---|
| Díaz Sanzo, Óscar | CSIC | R2 |
| Gutiérrez de Terán, Hugo | CSIC | R4 |
| Mateos Pinilla, Lucas | CSIC | No Classification |
| Sjöberg, David | Uppsala University | R1 |
In 2007, Hugo Hutiérrez de Terán created the Structural Bioinformatics Unit at the Galician Public Foundation for Genomic Medicine in Santiago de Compostela, where he began working on the study of the mechanism and regulation of G protein-coupled receptors (GPCRs) and the development of drugs for several of these receptors, developing his own methodologies such as the server for modeling these GPCR-ModSim receptors . In 2012, the laboratory migrated to Uppsala, where over the next 12 years, 7 PhD students and 4 postdoctoral students were trained, all of whom continued their biopharmaceutical careers in both the public and private sectors, most of them in R&D, and around 20 Master’s students from various European universities. During this time, he combined his interest in the pharmacology of GPCRs with the design of computational methods for drug screening and optimization based on structures and first principles physical simulation. His methodology for estimating drug-protein affinities and the effects of protein mutations stands out, using efficient protocols for the so-called free energy perturbation (FEP), Q-FEP , whose development he continues to coordinate with the collaboration of several international centers. As an open-source academic project, commercial exploitation for the high-throughput screening required by companies is managed through Modsim Pharma , the spin-off company co-founded by Hugo.
After obtaining a position as a Senior Scientist at the CSIC in 2021, he returned to Spain in 2024 to establish his laboratory within ISPA. The laboratory’s current and future priorities focus on the search for new small molecules as cancer immunotherapy through polypharmacological strategies; the discovery of new membrane receptor modulators through allosteric modulation mechanisms; and delving deeper into the mechanisms of both pathogenic mutations, in the context of genetically based diseases, as well as their effects on treatment resistance, with implications for personalized medicine.
- New strategies in cancer immunotherapy based on polypharmacology
Current immuno-oncology treatments are mainly based on expensive monoclonal antibodies and exhibit success rates of around 50%. Therefore, there is a growing biopharmaceutical interest in developing small molecules targeting immune metabolism that complement existing immuno-oncology therapies. This project addresses the characterization and therapeutic intervention of the adenosine receptor (AR) A 2B , a G protein-coupled receptor (GPCR) that is part of the purinergic signaling pathway commonly altered in various tumors. Compared to A2AAR antagonists in clinical trials, A2BAR blockade is a selective mechanism of therapeutic intervention, since this receptor is silenced under physiological conditions. We will identify and optimize high-affinity antagonists for A2BAR and develop them within a multi-target strategy that includes A2AAR, CD73 and the GPCR P2Y1, to obtain poly-inhibitors of the purinergic signaling system. This strategy is based on our recently published data and promising compounds in clinical trials, showing dual A2A/A2Baffinity .
- More precise pharmacological profiles for membrane receptor modulation
Our laboratory is working on the creation of predictive models for the latest paradigms in pharmacological modulation strategies for GPCRs: allosteric modulation and biased modulators (targeting a particular biochemical pathway), strategies with greater pharmacotherapeutic precision and reduced side effects. While the discovery of most allosteric modulators is due to serendipity, in our group we develop proprietary methods for locating potential allosteric regulatory sites that enable the rational, structure-based design of new allosteric modulators. To obtain biased modulators with new pharmacological profiles, we start from our model of receptor activation based on thermodynamic cycles, which has allowed us to move from classic antagonists (blockers) to agonists (activators) of adenosine receptors. A model that has inspired other software and pharmaceutical companies to use similar approaches, and that will allow us to identify novel chemical structures for specific types of modulation, with the resulting potential for transfer and patentability.
- Effect of mutations on the structure or function of proteins
A mutation can be spontaneous, inherited, or induced; it can occur in an organism or be induced in the laboratory. In any of these cases, a single mutation can affect the folding, structure, or function of a protein in a variety of ways. The effects can also be varied: from pathogenic mutations to causing drug resistance in various chemotherapy treatments in oncology or infectious diseases. Genetic engineering is potentially interesting in achieving super-stable structures or immobilizing proteins in a specific state to facilitate, for example, the experimental determination of their three-dimensional structure. In order to understand the molecular basis of these mechanisms, our group has developed an approach based on the appropriate representation of each of these processes through a thermodynamic cycle, which we solve using our own extremely efficient methodology and combine with artificial intelligence techniques, allowing us to characterize and anticipate pathogenic mutations responsible for resistance or that alter the conformational equilibrium of proteins, with the resulting applications in the areas of biomedicine or biotechnology.
- Tandarić, T and Gutiérrez-de-Terán, H.* Ligand and Residue Free Energy Perturbations Solve the Dual Binding Mode Proposal for an A2BAR Partial Agonist. J. Phys. Chem. B (2025) 119:886
- Aranda García, D. et al (including Gutiérrez-de-Terán, H.) and Selent, J. Large scale investigation of GPCR molecular dynamics data uncovers allosteric sites and lateral gateways. Nat Commun (2025) 16:2020
- Conflitti, P.; Lyman, E.; Sansom, M.S.P.; Hildebrand, P.W.; Gutiérrez-de-Terán, H.; Carloni, P.; Ansell, T.B.; Yuan, S.; Barth, P.; Robinson, A.S.; Tate, C.G.; Gloriam, D.; Grzesiek, S.; Eddy, M.T.; Prosser, S.; Limongelli, V. Functional dynamics of G protein-coupled receptors reveal new routes for drug discovery. Nat. Rev. Drug Discov. (2025) https://doi.org/10.1038/s41573-024-01083-3
- van den Broek, R.L.; Bello, X.; Küpper, R.V.; van Westen, G.J.P.; Jespers, W.; Gutiérrez-de-Terán, H.*GPCR-ModSim: Modelling and simulation of membrane proteins in a nutshell. Bioinformatics (2024) btae66.2
- Prieto-Díaz, R.n; Fojo-Carballo, H.; Majellaro, M.; Tandaric, T.; Azuaje, J.; Brea, J.; Loza, M.I.; Barbazan, J.e; Salort, G.; Chotalia, M.; Rodriguez-Pampin, I.; Mallo-Abreu, A.; Paleo, M. R.; Garcia-Mera, X.; Ciruela, F.; Gutiérrez-de-Terán, H.;‡ Sotelo, E.‡ Biginelli-Based Scaffold Hopping Approaches Unveil Novel A2B Adenosine Receptor Antagonist Chemotypes for Colorectal Cancer. Biomedicine & Pharmacotherapy (2024) 173:116345
- Anazia, K.; Koenekoop, L.; Ferré, G.; Petracco, E.; Gutiérrez-de-Teran, H;‡.; Eddy, M.T.‡ Visualizing the impact of disease-associated mutations on G protein-nucleotide interactions. J Biol Chem. (2024) 8:107497
- Prieto-Díaz, R.; González-Gómez, M.; Fojo-Carballo, H.; Azuaje, J.; El Maatougui, A.; Majellaro, M.; Loza, M.I.; Brea, J.; Fernández-Dueñas, V.; Paleo, R.; Díaz-Holguín, A.; Garcia-Pinel, B.; Mallo-Abreu, A.; Estévez, J.C.; Andújar-Arias, A.; García-Mera, X.; Gomez-Tourino, I.; Ciruela, F.; Salas, C.O.; Gutiérrez-de-Terán, H.;‡ Sotelo, E.‡ Exploring the Effect of Halogenation in a Series of Potent and Selective A2B Adenosine Receptor Antagonists. J. Med. Chem. (2023) 66:890
- BJ Bongers, M Gorostiola González, X Wang, HWT van Vlijmen, W Jespers, H Gutiérrez-de-Terán, K Ye, AP IJzerman, LH Heitman, GJP van Westen. Pan-cancer functional analysis of somatic mutations in G protein-coupled receptors. Sci. Rep. (2022) 12:21534
- Apple Hui Min Tay, Rubén Prieto-Díaz, Shiyong Neo, Le Tong, Xinsong Chen, Valentina Carannante, Björn Önfelt, Johan Hartman, Felix Haglund, Maria Majellaro, Jhonny Azuaje, Xerardo Garcia-Mera, Jose M Brea, Maria I Loza, Willem Jespers, Hugo Gutierrez-de-Teran, Eddy Sotelo, and Andreas Lundqvist. A2B adenosine receptor antagonists rescue lymphocyte activity in adenosine-producing patient-derived cancer models. J Immunother Cancer. (2022) 10: e004592
- Val, C.; Rodríguez-García, C.; Prieto-Díaz, R.; Crespo, A.; Azuaje, J.; Carbajales, C.; Majellaro, M.; Díaz-Holguín, A.; Brea, J.M.‡; Loza, M.I.; Gioé-Gallo, C.; Contino, M.; Stefanachi, A.; García-Mera, X.; Juan C Estévez, J.C.; Gutiérrez-de-Terán, H.‡ Sotelo, E.‡ Optimization of 2-Amino-4,6-diarylpyrimidine-5-carbonitriles as Potent and Selective A1 Antagonists. J. Med. Chem. (2022) 65:2091–2106
- Wei, S.; Thakur, N.; Ray, A.P.; Jin, B.; Obeng, S.; McCurdy, C.R.; McMahon, L.R.; Gutiérrez-de-Terán, H.; Eddy, M.T.; Lamichhane, R. Slow Conformational Dynamics of the Human A2A Adenosine Receptor are Temporally Ordered. Structure (2022) 30:329
- Jespers, ; Heitman, L.H.; IJzerman, A.P.; Sotelo, E.; van Westen, G.J.P.; Åqvist, J.; Gutiérrez-de-Terán, H.‡ Deciphering conformational selectivity in the A2A adenosine G protein-coupled receptor by free energy simulations. PLoS Comp. Biol. (2021) 17:e1009152
- Wang, X.; Jespers, W., Prieto, R.; Majellaro, M.; IJzerman, A.P.; van Westen, G.J.P.; Sotelo, E. ‡; Heitman L.H. ‡; Gutiérrez-de-Terán, H.‡ Identification of V6.51L as a selectivity hotspot in stereoselective A2B adenosine receptor antagonist recognition. Sci. Rep. (2021) 11:14171
- Cruz-López, O.; Ner, M.; Nerín-Fonz, F.; Jiménez-Martínez, ; Araripe, D.; Marchal, J.A.; Boulaiz, H.; Gutiérrez-de-Terán, H.; Campos, J.M.; Conejo-García, A. Design, synthesis, HER2 inhibition and anticancer evaluation of new substituted 1,5-dihydro-4,1-benzoxazepines. J Enz Inh Med Chem (2021) 36:1553–1563
- Vanga, S.R., Hallberg, A., Åqvist, J.; Gutiérrez-de-Terán, H.‡ Structural Basis of Inhibition of Human Insulin-Regulated Aminopeptidase (IRAP) by benzopyran-based inhibitors (2021) Frontiers Mol. Biosci. 8:625274
- Majellaro, M.; Jespers, W.; Crespo, A.; Núñez, M.J.; Novio, S.; Garcia-Santiago, C.; Azuaje, J.; Gioé, C.; Prieto, R.; Brea, J.‡; Loza, M.I; García-Mera, X.; Caamaño, O.: El Maatougui, A.; Mallo-Abreu, A.; Freire-Garabal, M.; Sardina, F.J.; Stefanachi, A.; Åqvist, J.; Gutiérrez-de-Terán, H.‡; Sotelo E.‡ 3,4-Dihydropyrimidin-2(1H)-ones as Antagonists of the Human A2B Adenosine Receptor: SAR Studies, Enantiospecific Recognition and Evidences of Antimetastatic Effect. (2021) J. Med. Chem. 64:458
- Jespers, W; Verdon, G; Azuaje, J; Majellaro, M.; Keränen, H.; García-Mera, X. Congreve, M.; Deflorian, F.; de Graaf, C.; Zhukov A.; Dore, A.; Mason, J.S.; Åqvist, J.; Cooke, R.M.; Sotelo, E.; Gutiérrez-de-Terán, H.‡ (2019): X-Ray Crystallography and Free Energy Calculations Reveal the Binding Mechanism of A2A Adenosine Receptor Antagonists. Ang. Chem Int Ed (2020) 59:16536-16543
- Vasile, S.; Sallander, J.; Hallberg, M.; Hallberg, A.; Åqvist, J.; and Gutiérrez-de-Terán, H.‡ Evolution of Angiotensin Peptides and Peptidomimetics as AT2 Receptor Agonists. Biomolecules (2020) 10:649
- Mallo-Abreu A, Prieto-Díaz R, Jespers W, Azuaje J, Majellaro M, Velando C, García-Mera X, Caamaño O, Brea J, Loza MI, Gutiérrez-de-Terán H,‡ Sotelo E.‡ A Nitrogen-Walk Approach to Explore Bioisosteric Replacements in a Series of Potent A2B Adenosine Receptor Antagonists. J. Med. Chem. (2020) 63:7721-7739
- Rodríguez-Espigares I, Torrens-Fontanals M, Tiemann JKS, Aranda-García D, Ramírez-Anguita JM, Stepniewski TM, Worp N, Varela-Rial A, Morales-Pastor A, Medel-Lacruz B, Pándy-Szekeres G, Mayol E, Giorgino T, Carlsson J, Deupi X, Filipek S, Filizola M, Gómez-Tamayo JC, Gonzalez A, Gutiérrez-de-Terán H, Jiménez-Rosés M, Jespers W, Kapla J, Khelashvili G, Kolb P, Latek D, Marti-Solano M, Matricon P, Matsoukas MT, Miszta P, Olivella M, Perez-Benito L, Provasi D, Ríos S, R Torrecillas I, Sallander J, Sztyler A, Vasile S, Weinstein H, Zachariae U, Hildebrand PW, De Fabritiis G, Sanz F, Gloriam DE, Cordomi A, Guixà-González R, Selent J. GPCRmd uncovers the dynamics of the 3D-GPCRome. Nature Methods (2020) 17:777-787
- Adenosine receptors as target in immune oncology
Code: PID2023-150793OB-I00A.
IP: Hugo Gutiérrez de Terán Castañón.
Institution: Centro de Investigación de Nanomateriales y Nanotecnología.
Duration: 1/9/2024-31/8/2027.
Funding: 250.000 €. - National Academic Infrastructure for Supercomputing-NAISS
IP: Hugo Gutierrez de Teran Castañon.
Institution: Uppsala University, Cell and Molecular Biology
Duration: 1/1/2024- 31/12/2024
Computing time valued on 500.000 €. - Validation for commercialization (VFT 1922)
Simulation package for PI: Hugo Gutierrez de Teran Castañon
Institution: Uppsala University, Cell and Molecular Biology
Duration: 9/12/2019-1/5/2021.
Funding: 50.000 €.
| PhD Student | Directors | Title | Year | Centers |
|---|---|---|---|---|
| Lucien Koenekoop | Johan Åqvist y Hugo Gutiérrez de Terán | Computational Study of Cold and Warm Adapted Proteins | 2025 | Uppsala University |
| Florian van der Ent | Johan Åqvist y Hugo Gutiérrez de Terán | Computational Studies of Psychrophilic Enzymes. | 2024 | Uppsala University |
| Willem Jespers | Hugo Gutiérrez de Terán y Johan Åqvist | Free energy calculations of G protein-coupled receptor modulation: New methods and applications | 2020 | Uppsala University |
| Silvana Vasile | Hugo Gutiérrez de Terán y Johan Åqvist | Computational prediction of ligand binding in peptide G-protein coupled receptors | 2019 | Uppsala University |
| Sudarsana Reddy Vanga | Hugo Gutiérrez de Terán y Johan Åqvist | Probing Ligand Binding Mechanisms in Insulin-Regulated Aminopeptidases: Computational analysis and free energy calculations of binding modes. | 2019 | Uppsala University |
| Jaka Sočan | Johan Åqvist y Hugo Gutiérrez de Terán | Enzyme Cold Adaptation through Evolution of Protein Flexibility. | 2019 | Uppsala University |
| Yashmin Shamsudin Kahn | Johan Åqvist y Hugo Gutiérrez de Terán | Non-Steroidal Anti-Inflammatory Drugs in Cyclooxygenases 1 and 2: Binding modes and mechanisms from computational methods and free energy calculations. | 2017 | Uppsala University |
| David Rodríguez Díaz | Hugo Gutiérrez de Terán y Ángel Carracedo | Computational Approaches for the Characterization of the Structure and Dynamics of G Protein-Coupled Receptors:Applications to Drug Design | 2012 | Universidade de Santiago de Compostela (USC) |
