Protein Crystallization for Structure-Based Drug Design

The crystallization experiment has one main objective: to obtain diffraction quality crystals. This can be achieved through myriad avenues; here the focus will be on crystallization in support of drug discovery. In drug discovery there are two main paradigms for crystallography: high-throughput, and by any means necessary. Each paradigm requires the investigator to formulate strategies based on different priorities. In the high-throughput environment, the emphasis is on rapid prosecution of a large number of protein targets. In the by any means necessary paradigm the target pool is generally smaller and structural information is absolutely necessary for success. The process of growing diffraction quality protein crystals involves deciding on a crystallization method, initial screening, cryoprotection, initial diffraction analysis, and growth optimization. Furthermore, in structure-based drug design it is necessary to obtain crystal structures of protein–ligand complexes.