Protein Biophysics for Drug Discovery

The Protein Biophysics for Drug Discovery area at iBET has over 20 years of experience in structure-based drug design in pre-clinical research, integrating dedicated protein production, biophysical characterization, molecular interactions functional studies, and X-ray crystallography.

iBET’s protein biochemists address specific needs in drug discovery programs, employing extensive experience with a broad range of protein modalities. These include soluble proteins to multi-component complexes fused with different affinity, detection, and functional tagging systems. We have developed a protein expression screening platform for bacterial, insect and mammalian cell cultures (both suspension and adherent) enabling customized design of large-scale production processes optimized for maximum protein productivity. This platform supports structural and activity studies. 

Protein construct design is supported by Limited Proteolysis approaches, complemented by our Mass Spectrometry services, which is routinely used to evaluate the most stable protein construct boundaries for production, activity and structural studies.  

Over the last 20 years, we have consolidated our expertise in structure-based drug discovery spanning from Hit Discovery to Clinical Candidates, both for small molecules and epitope mapping. We combine high quality protein production with biophysical characterization tools to support the integrated application of Biochemical and Cellular Assays, Molecular Interaction and Structural studies. We employ X-ray crystallography and different biophysical methods for protein characterization, target, and ligand binding mode elucidation. With our expertise we contribute to improve the understanding of protein structure and function and accelerate drug discovery programs with academic and industry partners. 

The team has in-house access to automated nano-crystallization setup and visualization, crystal optimization screenings and X-ray diffraction equipment, in addition to regular access to beamlines at European Synchrotron facilities. 

At iBET we use state-of-the-art facilities featuring advanced tools for drug discovery and the study of molecular interactions with selected drug targets. We are experts in medium to high-throughput characterization of small molecules, large fragment libraries, and antibodies.  

Our cutting-edge technologies and expertise include Surface Plasmon Resonance (SPR), Differential Scanning Fluorimetry (nDSF, TSA), Dynamic Light Scattering (DLS), Thermal Shift Assay (TSA), Microscale thermophoresis (MST) and Hydrogen/Deuterium Exchange-Mass Spectrometry (HDX-MS). By integrating these methodologies, along with our innovative Extract2Chip technology for studying challenging proteins by SPR without the need for protein purification, we provide comprehensive solutions to support pre-clinical research and enhance drug discovery and development. 

iBET offers a platform for biochemical and cellular assay development applied to early drug discovery. Starting with assay design, optimization, and validation, and ending with transposition for high-throughput formats through assay miniaturization, this platform is designed to screen compounds or ligands of pharmaceutical interest that modulate enzymatic activities or protein-protein interactions. Additionally, cell-based assays have been devised to access ligand binding to targets of interest within the cellular context. These assays are developed and implemented at iBET on a low and medium-throughput scale, facilitating in-house compound testing.