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Updated: Jun 27, 2026

Improving the Success Rate of Protein Crystallization by Random Microseed Matrix Screening
Published on: August 31, 2013
The role of bias in crystallization conditions in automated microseeding
Franz J St John1, Bo Feng, Edwin Pozharski
1Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore 21201, USA.
Abstract:
The automated microseeding protocol previously proposed by D'Arcy et al. [D'Arcy et al. (2007), Acta Cryst. D63, 550-554] includes an inherent chemical shift in all conditions in a sparse-matrix screen. This results from the uniform addition of mother liquor used to stabilize the microcrystalline seed stock, which is usually the mother liquor that resulted in successful crystal growth. It was found that there is an overlap in identified crystallization leads between addition of seed and addition of the mother liquor used to stabilize the seed. This indicates that additional crystallization ;hits' primarily (but not exclusively) arise from changes in the drop composition, not the introduction of seeds. A complementary automated microseeding protocol is proposed as a novel approach for biasing drops in a screen with many of the most popular precipitants.
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