CrystalCure: AI-based design of crystalline therapeutic proteins

Sergei Grudinin

Sergei GRUDININ,
DR CNRS,
Sergei.Grudinin@univ-grenoble-alpes.fr

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Jacques-Philippe COLLETIER
Jacques-Philippe COLLETIER,
DR CNRS,
colletier@ibs.fr

Website





DESCRIPTION

The CrystalCure project aims to develop an innovative strategy that combines artificial intelligence (AI)-based design of symmetrical protein interfaces with the exploitation of low-complexity regions (LCR; see below), to recombinantly produce crystalline formulations of therapeutic proteins in vivo.

The project builds on the expertise of the computational partners in AI-based protein bioinformatics (Sergei GRUDININ, LJK/UGA, and Pablo CHACÓN, IQF-Madrid) and the biological partners (Jacques-Philippe COLLETIER, IBS/CEA, and Leila SLAMTI, MICALIS) in the screening of, and structure determination from, nanocrystals produced by recombinant expression in Bacillus thuringiensis.

Our project has the potential to bring about transformative changes in the design, production, storage, formulation, cost, and diversity of protein therapeutics.

ACTIVITIES

  • A PhD student will be hired in Dr. Grudinin's lab starting in December 2025
  • An engineer will be hired in Dr. Colletier's lab in 2025–2026

SELECTED LIST OF PUBLICATIONS

  • Ritchie, D. W., & Grudinin, S. (2016). Spherical polar Fourier analysis of protein complexes with arbitrary point group symmetry. Applied Crystallography, 49(1), 158–167.
  • Colletier JP, Sawaya MR, Gingery M, Rodriguez JA, Cascio D, Brewster AS, Michels-Clark T, Hice RH, Coquelle N, Boutet S, Williams GJ, Messerschmidt M, DePonte DP, Sierra RG, Laksmono H, Koglin JE, Hunter MS, Park HW, Uervirojnangkoorn M, Bideshi DK, Brunger AT, Federici BA, Sauter NK, Eisenberg DS. (2016) De novo phasing with X-ray laser reveals mosquito larvicide BinAB structure. Nature, 539(7627):43-47. doi: 10.1038/nature19825. Epub 2016 Sep 28.
  • Pagès, G., Kinzina, E., & Grudinin, S. (2018). Analytical symmetry detection in protein assemblies. I. Cyclic symmetries. Journal of Structural Biology, 203(2), 142–148
  • Pagès, G., & Grudinin, S. (2018). Analytical symmetry detection in protein assemblies. II. Dihedral and cubic symmetries. Journal of Structural Biology, 203(3), 185–194.
  • Gao, Z., Tan, C., Chacón, P., & Li, S. Z. (2022). Pifold: Toward effective and efficient protein inverse folding. arXiv preprint arXiv:2209.12643.
  • Tetreau G, Sawaya MR, De Zitter E, Andreeva EA, Banneville AS, Schibrowsky NA, Coquelle N, Brewster AS, Grünbein ML, Kovacs GN, Hunter MS, Kloos M, Sierra RG, Schiro G, Qiao P, Stricker M, Bideshi D, Young ID, Zala N, Engilberge S, Gorel A, Signor L, Teulon JM, Hilpert M, Foucar L, Bielecki J, Bean R, de Wijn R, Sato T, Kirkwood H, Letrun R, Batyuk A, Snigireva I, Fenel D, Schubert R, Canfield EJ, Alba MM, Laporte F, Després L, Bacia M, Roux A, Chapelle C, Riobé F, Maury O, Ling WL, Boutet S, Mancuso A, Gutsche I, Girard E, Barends TRM, Pellequer JL, Park HW, Laganowsky AD, Rodriguez J, Burghammer M, Shoeman RL, Doak RB, Weik M, Sauter NK, Federici B, Cascio D, Schlichting I, Colletier JP. (2022). De novo determination of the mosquito-killing Cry11Aa and Cry11Ba structures from naturally occurring nanocrystals. Nat Commun., 13(1):4376. doi: 10.1038/s41467-022-31746-x.
  • Tetreau G, Banneville AS, Andreeva EA, Brewster AS, Hunter MS, Sierra RG, Teulon JM, Young ID, Burke N, Grünewald TA, Beaudouin J, Snigireva I, Fernandez-Luna MT, Burt A, Park HW, Signor L, Bafna JA, Sadir R, Fenel D, Boeri-Erba E, Bacia M, Zala N, Laporte F, Després L, Weik M, Boutet S, Rosenthal M, Coquelle N, Burghammer M, Cascio D, Sawaya MR, Winterhalter M, Gratton E, Gutsche I, Federici B, Pellequer JL, Sauter NK, Colletier JP. (2020) Serial femtosecond crystallography on in vivo-grown crystals drives elucidation of the mosquito-killing Cyt1Aa bioactivation cascade. Nat Commun., 11(1):1153. doi: 10.1038/s41467-020-14894-w.
Published on October 13, 2026
Updated on October 13, 2026