Recent progress in robot-based systems for crystallography and their contribution to drug discovery

Abstract

Introduction: X-ray crystallography is the main tool for macromolecular structure solution at atomic resolution. It provides key information for the understanding of protein function, opening opportunities for the modulation of enzymatic mechanisms, and protein–ligand interactions. As a consequence, macromolecular crystallography plays an essential role in drug design, as well as in the a posteriori validation of drug mechanisms.

Areas covered: The demand for method developments and also tools for macromolecular crystallography has significantly increased over the past 10 years. As a consequence, access to the facilities required for these investigations, such as synchrotron beamlines, became more difficult and significant efforts were dedicated to the automation of the experimental setup in laboratories. In this article, the authors describe how this was accomplished and how robot-based systems contribute to the enhancement of the macromolecular structure solution pipeline.

Expert opinion: The evolution in robot technology, together with progress in X-ray beam performance and software developments, contributes to a new era in macromolecular X-ray crystallography. Highly integrated experimental environments open new possibilities for crystallography experiments. It is likely that it will also change the way this technique will be used in the future, opening the field to a larger community.

Keywords::

• automation
• macromolecular X-ray crystallography
• robotics
• structural biology
• synchrotron beamlines

Acknowledgments

Most of the developments were made possible by the support of FIP-BM30A beamline (ESRF) technical and scientific staff, with the collaboration of the laboratory of S Cole at the École polytechnique Fédérale de Lausanne (EPFL, Lausanne, Switzerland), the “Centre de Biochimie Structurale” (Montpellier, France), and NatX-ray SAS (Saint Martin d’Hères, France). Much of this work was only possible thanks to excellent technical, engineering, and software support from the ESRF structural biology group, instrument services, development division, precision engineering laboratory and beamline control unit.

Notes

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