Merck Portugal sponsors the purchase of a new Protein Crystallization Robot by iBET


Founded in 1989 as a Research and Development (R&D) institution dedicated to building bridges between academia and industry, iBET is now the largest non-profit private Portuguese institution dedicated to biotechnology research and a global reference in the application of biotechnology to health and in the development of innovative and more effective vaccines, biopharmaceuticals and therapeutics.

iBET has been a partner of Merck KGaA in Darmstadt in drug discovery projects since 1994 as a supplier of pure samples of drug-target proteins. Since 2005, iBET is also a supplier of co-crystals with ligands designed by the medicinal chemists at Merck that have been previously validated as lead candidates by biophysical methods.

A fundamental part of the modern drug discovery process during hit-to-lead optimization consists of the crystallization of the target protein bound to the small molecule of interest or to highly specific antibodies. These crystals, with typical dimensions of 0.1 mm, are then used to obtain an atomic model of the protein-ligand complex by X-ray crystallography.

The ideal conditions for crystallizing each target protein are not known at project start, therefore a very large number of conditions must be tested. In order to do so efficiently and economically, minimizing the possibility of human error and the required amounts of protein, crystallization robots are used to set up the initial screenings in 96-well plates, in a matter of a few minutes. The volumes used (typically 0.0001 mL of protein solution per trial) are so small that in order to prevent evaporation it is necessary to carry out all the dispensing operations under a controlled humidity atmosphere. The plates are then sealed with a plastic film, stored in a temperature-controlled room, and inspected at regular intervals to check for the appearance of crystals. For each new crystallization project, up to 12 plates (exploring over 1,000 different crystallization conditions) may be prepared.

The robot presently used in the preparation of crystallization screens is nearing the end of its life cycle. Therefore, at the end of 2016 the iBET team approached the management of Merck Portugal with a request to support the purchase of a new robot, a key instrument in the continued partnership between the Structural Biology for Drug Discovery Unit at iBET in Oeiras and the Molecular Interactions and Biophysics Group at Merck in Darmstadt.

The selected instrument is a Mosquito® LCP and will be supplied by the British company TTP Labtech. In addition to the automated setup of vapor diffusion crystallization screens, the Mosquito® LCP includes the added functionality of dispensing lipidic cubic phase (LCP) plates used nowadays for membrane proteins, thus paving the ground for supporting future Merck projects targeting this type of proteins.

Both teams are grateful to the management of Merck Portugal for this strong display of support to their partnership.