Bioinformatics and CryoEM


The introduction of intuitive graphical software has enabled structural biologists who are not experts in crystallography to build complete protein or nucleic acid models rapidly. In contrast, carbohydrates are in a completely different situation: scant automation exists, and users building models manually frequently trip over legacy issues such as incorrect dictionaries or non-standard atom naming, which evidence a historical lack of methodological support for carbohydrates. Sugars are stereochemically complex and, as pyranose rings, have clear conformational preferences. And despite this, all refinement programs may produce high-energy conformations at medium to low resolution, without any support from the electron density; this problem renders the affected structures unusable in glyco-chemical terms. Bringing structural glycobiology up to ‘protein standards’ is thus requiring a total methodological overhaul. Time is of the essence, as the community is steadily increasing the production rate of glycoproteins, and electron cryo- microscopy has just started to image them in precisely that resolution range where crystallographic methods falter most. In this talk, I will introduce our latest methodological developments, designed to streamline and automate hitherto error-prone processes, effectively aiding crystallographers and electron microscopists alike in producing correct atomic models with confidence.

Some references in chronological order

- Agirre, J., Davies, G., Wilson, K., & Cowtan, K. (2015). Carbohydrate anomalies in the PDB. Nature chemical biology, 11(5), 303. – Agirre, J., Iglesias-Fernández, J., Rovira, C., Davies, G. J., Wilson, K. S., & Cowtan, K. D. (2015). Privateer: software for the conformational validation of carbohydrate structures. Nature Structural and Molecular Biology, 22(11), 833. – Hudson, K. L., Bartlett, G. J., Diehl, R. C., Agirre, J., Gallagher, T., Kiessling, L. L., & Woolfson, D. N. (2015). Carbohydrate–aromatic interactions in proteins. Journal of the American Chemical Society, 137(48), 15152-15160. – Agirre, J., Davies, G. J., Wilson, K. S., & Cowtan, K. D. (2017). Carbohydrate structure: the rocky road to automation. Current opinion in structural biology, 44, 39-47. – McNicholas, S., & Agirre, J. (2017). Glycoblocks: a schematic three-dimensional representation for glycans and their interactions. Acta Crystallographica Section D: Structural Biology, 73(2), 187-194. – Agirre, J. (2017). Strategies for carbohydrate model building, refinement and validation. Acta Crystallographica Section D, 73(2), 171-186.


Jon Agirre did a degree in Computer Engineering (San Sebastian, Spain) and received a PhD in Biochemistry (Bilbao, Spain) from the University of the Basque Country in 2009, and after short stages in the Institut de Biologie Structurale Jean-Pierre Ebel in Grenoble and Institut Pasteur in Paris (2011), went on to postdoctoral research in the Department of Chemistry of the University of York, where he continued the longtime tradition of crystallographic method development at York Structural Biology Laboratory (YSBL). In 2017 he received a Royal Society University Research Fellowship to work on new methodologies for carbohydrate structure modelling, refinement, validation and representation. He is the lead author of the Privateer, Sails and Glycoblocks software, and a major contributor to CCP4i2, the new graphical user interface for the CCP4 suite of programs.