MS02-04 - Automated, Remote-Controlled Ligand Screening Pipelines for Drug Discovery


Irina Cornaciu (EMBL Grenoble)

The evolution of automation in structural biology over the last decade has facilitated the study of challenging targets and extended the use of protein crystallography in drug discovery. However, manual crystal mounting and processing are time-consuming and resource-intensive, thus limiting the efficiency and productivity of small molecule screening in the context of drug design.  We have developed a new approach called CrystalDirect™, enabling automated crystal soaking, harvesting, and cryo-cooling. This technology offers a remarkable level of control during sample processing, making crystal mounting a more reliable and systematic operation that can easily deal with problematic crystal morphologies and sizes. It also provides higher tolerance to organic solvents during soaking experiments. Thanks to the CrystalDirect™ technology, we are providing access to an integrated pipeline including high-throughput crystallization, crystal soaking and mounting, and synchrotron data collection into a fully automated and continuous workflow. This pipeline can support very-fast analysis of small molecule-target complexes as well as easy and efficient large-scale fragment screening and is available to scientists from both in industry and academia. All the experimental information and results are tracked in real-time through CRIMS (the Crystallization Information Management System). Automated data processing through the Global Phasing Pipedream software suite - including data reduction, phasing, ligand fitting, and automated refinement - enables real-time data processing. The capabilities of this new technology and the experience gained from the use of these automated pipelines for ligand screening will be discussed.