title: Microseed matrix screening for optimization in protein crystallization: what have we learned?
abstract: Protein crystals obtained in initial screens typically require optimization before they are of X-ray diffraction quality. Seeding is one such optimization method. In classical seeding experiments, the seed crystals are put into new, albeit similar, conditions. The past decade has seen the emergence of an alternative seeding strategy: microseed matrix screening (MMS). In this strategy, the seed crystals are transferred into conditions unrelated to the seed source. Examples of MMS applications from in-house projects and the literature include the generation of multiple crystal forms and different space groups, better diffracting crystals and crystallization of previously uncrystallizable targets. MMS can be implemented robotically, making it a viable option for drug-discovery programs. In conclusion, MMS is a simple, time- and cost-efficient optimization method that is applicable to many recalcitrant crystallization problems.
authors.affiliation: Actelion Pharmaceuticals Ltd, Basel, Switzerland.
authors.forename: Allan
authors.initials: A
authors.lastname: D'Arcy
authors.affiliation: Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
authors.forename: Terese
authors.initials: T
authors.lastname: Bergfors
authors.affiliation: Novartis Institutes for Biomedical Research, Novartis Campus, 4056 Basel, Switzerland.
authors.forename: Sandra W
authors.initials: SW
authors.lastname: Cowan-Jacob
authors.affiliation: Swiss Light Source, Paul Scherrer Institute, 5232 Villigen PSI, Switzerland.
authors.forename: May
authors.initials: M
authors.lastname: Marsh
mesh_terms: D003460:Crystallization; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D011506:Proteins / Q000737:chemistry*
chemical_list: D011506:Proteins
keywords: crystallization; microseed matrix screening; optimization