Journal article

Bridging Crystal Engineering and Drug Discovery by Utilizing Intermolecular Interactions and Molecular Shapes in Crystals

Peter R Spackman, Li-Juan Yu, Craig J Morton, Michael W Parker, Charles S Bond, Mark A Spackman, Dylan Jayatilaka, Sajesh P Thomas

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | WILEY-V C H VERLAG GMBH | Published : 2019

Abstract

Most structure-based drug discovery methods utilize crystal structures of receptor proteins. Crystal engineering, on the other hand, utilizes the wealth of chemical information inherent in small-molecule crystal structures in the Cambridge Structural Database (CSD). We show that the interaction surfaces and shapes of molecules in experimentally determined small-molecule crystal structures can serve as effective tools in drug discovery. Our description of the shape and interaction propensities of molecules in their crystal structures can be used to screen them for specific binding compatibility with protein targets, as demonstrated through the high-throughput profiling of around 138 000 small..

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Grants

Awarded by Australian Research Council


Awarded by Danish National Research Foundation (Centre for Materials Crystallography)


Awarded by EU


Funding Acknowledgements

This work was supported by the Australian Research Council (DP130103304) and the Danish National Research Foundation (Centre for Materials Crystallography, DNRF93). SPT acknowledges EU funding for Marie Sklodowska-Curie Individual fellowship (grant number 798633).