Detalle de: Biomolecular Interactions & Structural Glycobiology Lab

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)