omation mbers - Society for Laboratory Automation and Screening

8:00 am Wednesday, February 4 Proteomics – Structural Room B1
Lance Stewart
deCODE genetics, Inc.
7869 N.E. Day Road West
Bainbridge Island, Washington 98110
lstewart@decode.com
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Co-Author(s)
Hidong Kim, Alexandrina Muntianu,
Geetha Sundaram, Mark Mixon,
Sattu Desai, Craig Sterling
Advanced Mixology: Liquid Handling Devices for High Speed Cocktail Preparation and
Iterative Protein-ligand Co-crystallization Experiments
Early stage drug discovery programs can be greatly accelerated by the availability of high-resolution X-ray crystal
structures of protein-ligand complexes. Ideally, multiple crystal structures of protein-ligand complexes are obtained
within three to nine months after the initiation of a drug development program. Unfortunately, there are numerous
bottlenecks between the selection of a target gene and the successful structure determination of a protein-ligand
co-crystal. To address several bottlenecks in the crystallization process, we have developed an integrated system
of secure database software and liquid handling robotics to automate the production, from stock solutions, of
the thousands of formulations that are required for iterative screening and optimization of protein crystal growth.
Protein-ligand co-crystallization screening is among the most demanding liquid handling applications in life
sciences. Protein samples and chemical libraries are expensive, sensitive to degradation, and are typically only
available in microgram to milligram quantities. Supply chain management of these materials is a challenge in and
of itself, not to mention the demands for small volume non-contact dispensing of complex formulations that have
varying viscosities, ionic strengths, chemical and pH gradients, etc. A typical crystallization experiment can often
require the properly sequenced random access microshot delivery of five or more solution components from
different source plates or vials (crystallization cocktail, protein, ligand, additive, reducing agent, metal co-factor,
allosteric modulator, a second protein, etc.). Our efforts to address these demanding liquid handling issues will be
described together with specific crystallization examples from our drug discovery programs.
8:30 am Wednesday, February 4 Proteomics – Structural Room B1
Frank Von Delft
The Scripps Research Institute
10550 North Torrey Pines Road-SR101
La Jolla, California 92037
loretta@scripps.edu
High Throughput Technologies in Structural Biology and Applications Towards Genomes,
Pathways, and Drug Design
Four years after the start of the development of high throughput structural proteomics, we are now observing
almost a dozen vendors manufacturing crystallization and imaging technologies. Significant improvements
in the other areas related to the structural biology processes are also being seen. Integration and efficiency
improvements based on data analysis remain as significant challenges, but new systems and approaches are
emerging. Given this history, we are starting to observe the first sets of results that have directly come from these
technological innovations. Lastly, both biotech and almost all members of the pharmaceutical industry are now
embracing high throughput structural proteomics technologies. A description of the current challenges and recent
successes will be presented.