42nd ECA Lunch webinar (23rd April 2026 13:00 CEST)

The ECA kindly invites you to the 42nd ECA Lunch webinar:

Knowledge of the three-dimensional structures of biological macromolecules plays a pivotal role in understanding fundamental life processes and in the development of novel pharmaceuticals. The intense X-rays available at modern synchrotron beamlines provide macromolecular crystallographers with an unparalleled tool for investigating biological phenomena at atomic resolution. The resulting structural insights into the mechanisms underlying biological processes have profoundly shaped biomedical sciences over the last three decades—often referred to as the “golden age” of structural biology.
Among the various techniques available for structure determination, macromolecular X-ray powder diffraction (XRPD) [1–2] has evolved over the past decades from an almost impossible dream into a robust and respected analytical method. XRPD can be employed in biosciences for multiple purposes, including the observation of phase transitions [3–4], characterization of bulk pharmaceuticals [5], accurate structure determination, and the detection of ligands in protein–ligand complexes [6].
This presentation highlights selected case studies that demonstrate the power of state-of-the-art infrastructures available at the ESRF, including:
• The investigation of molecular and crystal polymorphism in microcrystalline protein drugs against diabetes, aiming to improve therapeutic performance through the development of microcrystalline formulations and the combination of human insulin (HI) with pharmaceutically active organic ligands.
• Studies of the structure and dynamics of proteins from newly emerging, high-risk RNA viruses, with the goal of supporting antiviral drug design and exploring crystallographic fragment-screening as a powerful approach for the discovery of novel inhibitors. These studies contribute essential knowledge to EU projects focused on pandemic preparedness (EVA & VIZIER).
• The development and integration of methodologies for enhancing peptide-based drugs, providing crucial information to optimize absorption, distribution, metabolism, and excretion (ADME) properties through extensive peptide and protein polymorph screening.
• In situ investigations of pharmaceutical peptides and proteins under controlled variation of physicochemical parameters, such as relative humidity and temperature, offering unique insights into structural stability, hydration dynamics, and phase behavior; factors that are essential for optimizing formulation and storage conditions of therapeutic biomolecules [7-8].
Together, these studies illustrate the transformative potential of synchrotron-based techniques in pharmaceutical structural science, bridging the gap between molecular understanding and drug development.

References
1. Margiolaki, I., “Macromolecular Powder Diffraction”, Book Chapter for the International Tables of Crystallography- Volume H: Powder Diffraction, chapter 7.1, 718-736, (2019).
2. Karavassili, F. & Margiolaki I., (2016) Protein & Peptide Letters 23, 3, 232.
3. Spiliopoulou M. et al., J. Appl. Cryst. (2021). 54, 963.
4. Fili S. et al., IUCrJ. (2015). 4, 2, 534; Triandafillidis D. P. et al., Acta Cryst. D (2020). 76, 1065.
5. Karavassili F. et al., Biomolecules (2017). 7, 3, 63.
6. Margiolaki I. et al., J. Am. Chem. Soc. (2007). 129, 11865; Triandafillidis D. P. et al., Acta Cryst. D. (2023). 79, 374-386; Karavassili F. et al., Acta Cryst. D (2020). 76, 4, 375.
7. Athanasiadou M. et al., SynBio (2024), 2(2), 205-222.
8. Kontarinis A. et al., J. Appl. Cryst. (In Press), https://doi.org/10.1107/S1600576725007484