X-ray crystallography is the predominant method used to visualize biological macromolecules at an atomic level of detail. Crystals are mandatory for these structure determinations. The High-Throughput Crystallization Screening (HTS) Laboratory at the Hauptman-Woodward Institute is a community resource that provides crystallization information in a rapid and efficient manner so that structural investigations can rapidly progress. We have developed two sets of 1536 chemical cocktails designed to maximize crystallization potential and chemical solubility information for biological macromolecules for both structural and other scientific applications. In less than ten minutes, liquid-handling systems combine the community-provided sample with chemical cocktails in a single, compact, 1536-well plate. We image the experiments at weekly intervals for six weeks and provide users with immediate access to images. This includes software developed in-house, to view and analyze the results. We employ a state-of-the-art imaging system with a femtosecond pulse laser to detect crystals, including submicron crystals that are too small to see using traditional microscopy. If there are crystals, we are able to detect them. An expert reviews the outcomes for all samples sent to the laboratory to identify crystals and provides this information to the investigators. A graphical summary report provides investigators with relational chemical solubility and crystallization information in readily interpretable formats. The goal of the HTS Laboratory is to provide a rapid turnaround of solubility and crystallization information for community-provided samples to enable rapid scientific process. Our publication records, and associated publications and PDB depositions from structural genomics and the scientific community collaborations support our 15+ year history in the research, development and application of crystallization assays to more than 16,000 samples provided by hundreds of investigators.
X-ray crystallography is the predominant method used by scientists to visualize the machinery of life, biological macromolecules, whose interactions and operations determine the health of an individual. The structure/function paradigm drives our understanding of disease processes and treatments. We provide crystallization information for biological macromolecules, including technically challenging but therapeutically important membrane proteins, to rapidly move structural investigations forward to fulfill their greater purpose, to acquire new knowledge to help prevent, detect, diagnose, and treat disease and disability.
