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Updated: Aug 8, 2025

Author Spotlight: High-Throughput Screening to Obtain Crystal Hits for Protein Crystallography
Published on: March 10, 2023
Phage Display Screening as a Rational Approach to Design Additives for Selective Crystallization Control in
Benjamin Madeja1, Patrick Wilke2, Eduard Schreiner3
1Physical Chemistry, University of Konstanz, Universitätsstr. 10, D-78464, Konstanz, Germany.
Abstract:
The design of additives showing strong and selective interactions with certain target surfaces is key to crystallization control in applied reactive multicomponent systems. While suitable chemical motifs can be found through semi-empirical trial-and-error procedures, bioinspired selection techniques offer a more rationally driven approach and explore a much larger space of possible combinations in a single assay. Here, phage display screening is used to characterize the surfaces of crystalline gypsum, a mineral of broad relevance for construction applications. Based on next-generation sequencing of phages enriched during the screening process, a triplet of amino acids, DYH, is identified as the main driver for adsorption on the mineral substrate. Furthermore, oligopeptides containing this motif prove to exert their influence in a strictly selective manner during the hydration of cement, where the sulfate reaction (initial setting) is strongly retarded while the silicate reaction (final hardening) remains unaffected. In the final step, these desired additive characteristics are successfully translated from the level of peptides to that of scalable synthetic copolymers. The approach described in this work demonstrates how modern biotechnological methods can be leveraged for the systematic development of efficient crystallization additives for materials science.

