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Fabrice Gorrec

Fabrice Gorrec

Title: The Morpheus III protein crystallization screen: at the frontier of drug discovery

Biography

Biography: Fabrice Gorrec

Abstract

The original Morpheus screen has proven to be a very effi cient protein crystallization screen in the long term for a broad
variety of protein samples and the fi rst follow-up screen, Morpheus II starts to have an impact for many research groups.
Th e 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 fl ashfreezing
crystals are simplifi ed. Th e 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. Th e primarily aim however is
to obtain novel macromolecular crystals (with or without ligand observed in the structures). Th e fi nal 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 buff er systems to form the 3D grid.