The Biomolecular Interactions & Structural Glycobiology Group (BISG), located at the Institute of Chemical Research (IIQ-CSIC/University of Seville), investigates the chemistry of biomolecular recognition with the mission of facilitating an atomic-resolution understanding of biologically relevant biomolecular and biomaterial interactions from structural and dynamic perspectives.
The group specialises in the rational molecular design of new ligands, including both inhibitors and activators, targeted at biologically relevant proteins through the development of an integrated platform that combines cutting-edge experimental and computational methodologies. Central to this mission are pioneering advanced nuclear magnetic resonance (NMR) spectroscopy techniques and molecular modelling approaches that enable the rapid characterisation of weak protein-ligand complexes, structure-activity relationships, and the orientation of bioactive ligands at protein binding sites.
The laboratory has developed transformative technologies including NMR-based affinity determination using saturation transfer difference (STD), the DEEP-STD NMR method for ligand orientation, the RedMat and RedDat software platforms to accelerate the validation of 3D complexes and the mapping of binding epitopes, and the SHARPER NMR ultra-fast ligand ranking method for rapid prioritisation of ligand affinities—tools that significantly improve the efficiency of fragment-based and structure-guided drug discovery programmes. A distinctive research emphasis focuses on carbohydrate- and glycan-based systems, encompassing glycosaminoglycans, glycomimetics, and glycoprotein interactions, with applications ranging from immune receptor recognition and antimicrobial therapies to pathogenic infection mechanisms and enzyme catalysis.
Driven by significant international collaborations and evident recognition in publications in journals such as the Journal of the American Chemical Society, Angewandte Chemie, Nature Communications, and Nature Microbiology, among others, combined with expertise in machine learning-assisted NMR for the characterisation of protein-ligand interactions, the BISG group is developing a comprehensive set of experimental and computational tools to advance molecular design and accelerate the path from concept to validated therapeutic candidates.
Main research areas
- Structural chemistry of weak interactions assisted by advanced NMR and computational techniques for the molecular design of new bioactive molecular entities
- Development of cutting-edge NMR methodologies based on ligand observation techniques, and new computational approaches for the validation of 3D structures of protein-ligand complexes of bio- and pharmacological interest
- Artificial Intelligence for the acceleration and optimization of pharmacophores in the design of new drugs by STD NMR spectroscopy
- Structural chemistry for the molecular design of bacterial virulence factor inhibitors
- Structural chemistry for the molecular design of inhibitors of glycosyltransferase enzymes involved in cancer to accelerate the design of precision therapeutics
- Structural basis of the role of glycans in norovirus infection, towards new therapies based on human milk oligosaccharide mimetics (HMOs)
Pablo Valverde Sánchez
Postdoctoral Researcher
Adelyn María Betances Mora
PhD Student
Gabriel Rocha Domínguez
PhD Student
Henry Noah Flatau
PhD Student
Cristina Mora Cordero
Laboratory Technique
- J. C. Muñoz-García,* F. G. Moscoso, E. M. Sánchez-Fernández, J. Santos, J. Angulo, C. Carrillo-Carrión*. Insights into the Controlled Formation of Zr-Based Metal–Organic Gels: Linking Macroscopic Properties with Molecular Information from Solution State NMR.Angewandte Chemie International Edition (2026), e20987. https://doi.org/10.1002/anie.202520987
- J. Ramírez-Cárdenas, V. Taleb, V. Calvaresi, W.B. Struwe, S. El Qaidi, C. Zhu, K. Hasan, Y. Zhang, P.R. Hardwidge, B. Veloz, J.C. Muñoz-García, R. Hurtado-Guerrero, J. Angulo, STD NMR Epitope Perturbation by Mutation Unveils the Mechanism of YM155 as an Arginine-Glycosyltransferases Inhibitor Effective in Treating Enteropathogenic Diseases. JACS Au 5 (2025) 1279–1288. https://doi.org/10.1021/jacsau.4c01140.
- R. Nepravishta, J.C. Munoz-Garcia, K. Cameron, J. Angulo, D. Uhrin, Fast and Reliable NMR-Based Fragment Scoring for Drug Discovery. Journal of the American Chemical Society 147 (2025) 40296–40304. https://doi.org/10.1021/jacs.5c11092.
- S. Monaco, J. Browne, M. Wallace, J. Angulo, L. Stokes, On-Cell Saturation Transfer Difference NMR Spectroscopy on Ion Channels: Characterizing Negative Allosteric Modulator Binding Interactions of P2X7. Journal of the American Chemical Society 147 (2025) 32400–32411. https://doi.org/10.1021/jacs.5c02985.
- G. Rocha, J. Ramírez-Cárdenas, M.C. Padilla-Pérez, S. Walpole, R. Nepravishta, M.I. García-Moreno, E.M. Sánchez-Fernández, C. Ortiz Mellet, J. Angulo, J.C. Muñoz-García, Speeding-up the Determination of Protein–Ligand Affinities by STD NMR: The Reduced Data Set STD NMR Approach (rd-STD NMR) Analytical Chemistry 96 (2024) 615–619. https://doi.org/10.1021/acs.analchem.3c03980.
- R. Nepravishta, J. Ramírez-Cárdenas, G. Rocha, S. Walpole, T. Hicks, S. Monaco, J.C. Muñoz-García, J. Angulo, Fast Quantitative Validation of 3D Models of Low-Affinity Protein–Ligand Complexes by STD NMR Spectroscopy. Journal of Medicinal Chemistry 67 (2024) 10025–10034. https://doi.org/10.1021/acs.jmedchem.4c00204.
- A. Silva-Díaz, J. Ramírez-Cárdenas, J.C. Muñoz-García, M.C. de la Fuente, M. Thépaut, F. Fieschi, J. Ramos-Soriano, J. Angulo, J. Rojo, Fluorinated Man9 as a High Mannose Mimetic to Unravel Its Recognition by DC-SIGN Using NMR. Journal of the American Chemical Society 145 (2023) 26009–26015. https://doi.org/10.1021/jacs.3c06204.
- S. Monaco, J. Angulo, M. Wallace, Imaging Saturation Transfer Difference (STD) NMR: Affinity and Specificity of Protein–Ligand Interactions from a Single NMR Sample. Journal of the American Chemical Society 145 (2023) 16391–16397 https://doi.org/10.1021/jacs.3c02218.
- K. Malec, S. Monaco, I. Delso, J. Nestorowicz, M. Kozakiewicz-Latała, B. Karolewicz, Y.Z. Khimyak, J. Angulo, K.P. Nartowski, Unravelling the mechanisms of drugs partitioning phenomena in micellar systems via NMR spectroscopy. Journal of Colloid and Interface Science 638 (2023) 135–148. https://doi.org/10.1016/j.jcis.2023.01.063.
- V. Gabrielli, A. Kuraite, M.A. da Silva, K.J. Edler, J. Angulo, R. Nepravishta, J.C. Muñoz–García, Y.Z. Khimyak, Spin diffusion transfer difference (SDTD) NMR: An advanced method for the characterisation of water structuration within particle networks Journal of Colloid and Interface Science 594 (2021) 217–227. https://doi.org/10.1016/j.jcis.2021.02.094.
- S. Monaco, L.E. Tailford, N. Juge, J. Angulo, Differential Epitope Mapping by STD NMR Spectroscopy To Reveal the Nature of Protein–Ligand Contacts, Angewandte Chemie International Edition 56 (2017) 15289–15293. https://doi.org/10.1002/anie.201707682
- J.B. Park, Y.H. Kim, Y. Yoo, J. Kim, S.-H. Jun, J.W. Cho, S. El Qaidi, S. Walpole, S. Monaco, A.A. García-García, M. Wu, M.P. Hays, R. Hurtado-Guerrero, J. Angulo, P.R. Hardwidge, J.-S. Shin, H.-S. Cho, Structural basis for arginine glycosylation of host substrates by bacterial effector proteins, Nature Communications 9 (2018) 4283. https://doi.org/10.1038/s41467-018-06680-6
GlyCanDrug: A training network on the design of precision therapeutics that target key glycan motifs implicated in cancer
Project 101119601, HORIZON-MSCA-2022-DN-01 funded by:
Grant agreement ID:101119601
Entity: European Commission (251.971,00€)
PI: Jesús Angulo
Validity: 2023-2027
GlycoNoVi: Understanding the Role of Glycans in Human Norovirus Infection: a Key to Unlock New Therapies
Project 101072717 HORIZON-MSCA-2021-DN-01 funded by:
Grant agreement ID: 101072717
Entity: European Commission (251.971,00€)
PI: Jesús Angulo
Validity: 2023-2026
Learning to Design Sweet Renewable Hydrogels – Development of Experimental Protocols and Deep Learning Models to Decode Complex Structure-Function Relationships (Sweet2Gel)
Project HRZ-MSCA-2021-PF-01-101064251 funded by:
Grant agreement ID: 101064251
Entity: European Union, HORIZON-MSCA-2021-PF-01 (181.152,96€)
PI: Jesús Angulo (MSCA-PF Researcher: Juan Carlos Muñoz García)
Validity: 2022 – 2023
Machine Learning for Low Affinities — Towards Accelerating the Generation of NMR-validated Protein-Fragment Complexes and Glycomaterials Design
Project DGP_EMEC_2023_00169 funded by:
Reference: DGP_EMEC_2023_00169
Entity: Junta de Andalucía: Programa de Captación de Talento EMERGIA (235.340€)
PI: Dr. Juan C. Muñoz-García
Validity: 2025 – 2029
Machine Learning for the Acceleration and Optimization of Pharmacophores for the Design of New Medicines by STD NMR
Project MMT24-IIQ-01 funded by:
Reference: MMT24-IIQ-01
Entity: Programa Momentum-CSIC. Ministerio de Ciencia e Innovación/Ministerio para la Transformación digital y de la Función Pública (370.516,78€)
PI: Jesús Angulo
Validity: 2024 – 2028
Química estructural de interacciones biomol. débiles: STD NMR, Mutation Screening y Machine Learning para acceder al colectivo dinámico 3D. Inhibición de glicosiltransferasas
Project PID2022-142879NB-I00 funded by:
Reference: PID2022-142879NB-I00
Entity: Ministerio de Ciencia e Innovación/Agencia Estatal de Investigación (212.500,00 € + PhD contract)
PI: Jesus Angulo.
Validity: 2023 – 2026
A 19F-Protein and 1H-Ligand NMR toolkit to design inhibitors of bacterial virulence effectors
Project PY20_01176 funded by:
Reference: PY20_01176
Entity: Junta de Andalucía. Subvenciones a proyectos de I+D+i universidades y entidades públicas de investigación (90.000,00€)
PI: Jesús Angulo
Validity: 2020 – 2022
Nuevas Herramientas STD NMR para obtener Estructuras 3D de Complejos Proteina-Ligando Débiles: Aplicación a Interacciones Proteína-Carbohidrato Biológicamente Relevantes
Project PID2019-109395GB-I00 funded by:
Reference: PID2019-109395GB-I00
Entity: Ministerio de Ciencia e Innovación/Agencia Estatal de Investigación, Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (102.850,00€ + PhD contract)
PI: Jesús Angulo
Validity: 2020-2023