Journal of Proteomics & Bioinformatics
Open Access
ISSN: 0974-276X
+44 1223 790975
ISSN: 0974-276X
+44 1223 790975
Fabrice Gorrec
MRC Laboratory of Molecular Biology, UK
Scientific Tracks Abstracts: J Proteomics Bioinform
The original Morpheus screen has proven to be a very efficient protein crystallization screen in the long term for a broad variety of protein samples and the first follow-up screen, Morpheus II starts to have an impact for many research groups. The main ideas behind the formulation of Morpheus III were the same as originally to increase the chances of crystal nucleation and growth by integrating mixes of additives that can act as stabilizers, cross-linkers, etc. Follow systematic approaches to select the reagents and formulate the screen, such as the integration of ligands that are highly represented in the PDB and a 3D grid formulation. Consider pragmatic ways to facilitate structure solution. For example, the screening of cryoprotectants and flashfreezing crystals are simplified. The novelty in Morpheus III is the selection of small drug-like compounds as additives (average MW=248 Da). To some extent, the approach can be compared to fragment-based lead discovery. The primarily aim however is to obtain novel macromolecular crystals (with or without ligand observed in the structures). The final formulation of the new 96-condition crystallization screen integrates 44 compounds overall, divided into 8 mixes of additives. Each mix of additives is combined with 4 cryo-protected precipitant mixes and 3 buffer systems to form the 3D grid. Recent Publications 1. Gorrec F (2009) The Morpheus protein crystallization screen. Journal of Applied Crystallography 42:1035-1042. 2. Gorrec F (2015) The Morpheus II protein crystallization screen. Acta Crystallographica 71(7):831-837. 3. McPherson A and Cudney B (2006) Searching for silver bullets: an alternative strategy for crystallizing macromolecules. Journal of Structural Biology 156(3):387-406. 4. Gorrec F and Lowe J (2018) Automated protocols for macromolecular crystallization at the mrc laboratory of molecular biology. Journal of Visualized Experiments DOI: 10.3791/55790. 5. Blundell T L (2017) Protein crystallography and drug discovery: recollections of knowledge exchange between academia and industry. IUCr Journal 4:308-321.