Applied Biomolecular Sciences Unit (UCIBIO)
Faculty of Sciences and Technology
Universidade NOVA de Lisboa
Campus Caparica, 2829-516 Caparica, Portugal
» Cabrita Lab at NOVA
The main purpose of the Cabrita lab is the study of intermolecular interactions in chemical and biological systems to rationalize molecular recognition processes at atomic resolution. One of the key objectives is the study of protein-ligand interactions for the design, optimization and understanding of the action of drugs. For this purpose, we employ nuclear magnetic resonance techniques that allow to determine ligand epitopes and binding poses and to identify protein residues involved in recognition and binding, as well as changes in protein conformation and dynamics. This information allows to build structure/activity relationships, crucial to achieve a comprehensive understanding of the function of the systems studied. Recently our research efforts have been focused in the optimization of experimental conditions to study protein-ligand interactions of membrane proteins in close to native environments and in the study of glycan-protein interactions in systems related to aberrant glycosylation in cancer.
The key method used for research is nuclear magnetic resonance spectroscopy (NMR). Liquid-state NMR spectroscopy, allows for direct observations of NMR-active nuclei and can be employed to investigate the structures of small molecules or appropriately-labelled biomolecules. Most atomic nuclei in natural substances, with the exception of protons (1H), are NMR-insensitive and cannot be detected by NMR methods. Therefore, these nuclei are substituted with stable NMR active isotopes to make them NMR ‘visible’. Isotope labelling is a routine procedure in biomolecular NMR spectroscopy that usually requires labelling all residues of a protein with 13C and 15N. However, depending on the problem being investigated more sophisticated schemes have been devised to introduce NMR-active isotopes at specific protein positions (i.e. segmental labelling, site selective labelling), or at subsets of amino acid residues (i.e. residue-specific labelling). Together, these techniques allow us to either visualize whole proteins, or to engineer NMR observables at specific protein sites. With this tools NMR can directly assesses the conformational and functional properties of proteins in many different contexts.
Main areas of research
- Protein-ligand interactions with substrates and inhibitors
- Protein structure and dynamics
- Influence of the environment (solvent, osmolytes, salts, etc) in protein structure, dynamics and interactions