Our crystallographers have determined the structures of hundreds of proteins and protein complexes, guiding lead optimization for small molecule and biologic therapeutics. We use high intensity synchrotron X-ray sources, maximizing resolution of the final structure. Our expertise encompasses protein construct design, which can be a critical factor in the success of structure determination as well as in the relevance of the data.
Structure-Guided Drug Discovery
The structure of a protein:ligand complex reveals the molecular interactions governing ligand binding, and can show corresponding conformational changes in the protein. A co-structure provides experimental validation of the ligand’s mode of binding, and provides insights to guide optimization of the therapeutic lead.
An antibody:antigen structure is a definitive epitope map. Understanding the molecular basis of epitope binding is key for optimizing antibody affinity and specificity, which is of increasing interest with the rise of antibodies as therapeutics.
Fragment Based Screening (FBS)
FBS can identify low-molecular-weight ligands that bind to a target protein. These fragments can be grown, or multiple fragments can be joined together, to produce drug candidates in a rational way. Thermal shift analysis (TSA) or surface plasmon resonance (SPR) assays can be employed to identify fragment ligands, while X-ray structure determination of the target:ligand complex can guide the development of the fragments into drug candidates.