Joint Integrative Computational Biology workshop and CAPRI Meeting

Session

Protein conformational flexibility and solution experiments

13 Feb 2024, 13:45

IBS seminar room (EPN Campus)

39. Integrative ensemble modeling that utilizes distance distribution restraints

Gunnar Jeschke (ETH Zürich)

13/02/2024, 13:45

Talk

AlphaFold2 predictions for the human proteome reveal that the great majority of all human proteins contain intrinsically disordered regions (IDRs) or do not cotnain a folded domain at all. The structure of such proteins must be represented by an ensemble of conformers. However, most experimental techniques provide ensemble-average restraints, which do not contain direct information on width of...

18. Mechanistic study of MexAB-OprM efflux pump by an integrative approach

Isabelle Broutin (université Paris Cité)

13/02/2024, 14:10

Talk

Bacterial infections remain a major public concern due to the accelerated increase in the appearance of antibiotic resistance. Among the different mechanisms used by bacteria to resist to antibiotics, the active efflux plays a major role. In Gram-negative bacteria, this is achieved by tripartite efflux pumps that form a macromolecular assembly spanning both membranes of the cellular wall, the...

21. Challenges in visualizing structural flexibility of the SAGA complex

Gabor Papai (INSERM)

13/02/2024, 14:35

Talk

Cryogenic electron microscopy (cryo-EM) stands out as a widely utilized technique for elucidating the structures of macromolecular proteins. This method involves capturing projections of protein specimens embedded in thin, amorphous ice, preserving them within the vacuum of an electron microscope. The resulting structure emerges from the averaging of thousands of particle images, revealing...

16. Deciphering protein conformational dynamics with cryo-EM and MD simulations

Rémi Vuillemot (LJK, Université Grenoble Alpes, France)

13/02/2024, 15:00

Talk

Cryo-Electron Microscopy (cryo-EM) allows conformational studies of macromolecular complexes in their close-to-native state, essential for understanding their working mechanisms and for structure-based drug development. However, deciphering continuous conformational transitions of macromolecules, through the main cryo-EM processing techniques, Single Particle Analysis (SPA) and cryo-Electron...

47. Mariage of Cryo-EM, Solution Scattering, and Computational Science

Masaaki Sugiyama (Kyoto University, Institute for Integrated Radiation and Nuclear Science)

13/02/2024, 15:55

Talk

Over the past five years, structural biology has undergone a significant progress. The Nobel Prize in Chemistry awarded in 2017 to the developers of cryo-electron microscopy (cryo-EM) marked a milestone, and the rapid progress and widespread adoption of this technique have demonstrated that the precise structural analysis of biomacromolecules is not limited to crystallography or solution...

9. Protein Dynamics at extreme Temperatures

Beatrice CAVIGLIA (Universite' Paris Cite', University of Perugia)

13/02/2024, 16:20

Talk

Life has adapted to extreme conditions on Earth. One of the most striking evidences of adaptation to extreme environments are bacteria that are capable of thriving in a vast temperature range, from below 0° C in glacial waters to above 100° C in deep-sea hydrothermal vents. It is known that the individual molecular components of these organisms, exhibit enhanced stability and resistance to the...

32. POU5F1B and GOLPH3, two challenging proteins in structural biology

Dr Maria Marcaida (EPFL)

13/02/2024, 16:45

Talk

During this seminar, two experimental structural biology projects will be discussed illustrating current challenges and limitations in the field. The first will show how sequence identity may fail in predicting the protein structure and function. The second deals with investigating protein-protein interactions experimentally with the aim of creating small molecule inhibitors that block such...

37. Integrative structural biology of cell extracts : an application to structurally undercharacterized organisms

Ambroise Desfosses (CNRS- IBS)

13/02/2024, 17:40

Talk

Integrative structural biology of cell extracts bridges the gap between the high resolution structural characterisation of highly purified, isolated biomolecules and in situ electron tomography. This booming technique combines mass spectrometry (MS)-based proteomics and cryo-electron microscopy (cryo-EM) of fractionated cell extracts to quantitatively and structurally characterise endogenous...

10. Ensemble based calculations of spin-spin couplings in proteins: from ordered to disordered peptides

Amina Gaffour

13/02/2024, 18:05

Talk

To acquire a better understanding of how proteins work at the molecular level, it is crucial to understand their structural characteristics. Various techniques have been developed to achieve this, such as computer-based methods for calculating and predicting NMR measurements including the spin-spin coupling constants (SSCCs). Multi-scale calculations combining molecular dynamics simulations...

23. Hinge disulfides in human IgG2 CD40 antibodies modulate receptor signaling by regulation of conformation and flexibility

Hayden FISHER (ESRF)

13/02/2024, 18:30

Talk

The human IgG2 (hIgG2) isotype is unique in its ability to undergo redox based shuffling of its hinge disulfides. Previous work identified hIgG2 as the optimal isotype for mediating activation (agonism) of multiple tumour necrosis factor receptor superfamily (TNFRSF) members, with the hinge disulfides shown to be critical. CD40 is a co-stimulatory TNFRSF receptor that can be targeted using...

50. Intrinsically disordered regulators of endocytosis - an integrated NMR/single molecule fluorescence approach

Sigrid Milles (Forschungsverbund Berlin e.V. (FMP))

14/02/2024, 08:30

Talk

Intrinsically disordered proteins (IDPs) lack clearly defined structure and are therefore highly flexible and easily adaptable to different binding partners. This makes them important players in many biological processes, often with vital regulatory functions. Their dynamic features and broad range of interaction modes, however, render them difficult to study and analyzing their complexes...

8. The Influence of Globular Domains on an Intrinsically Disordered Region of p53: A Molecular Dynamics Investigation

Michael Bakker (Charles University)

14/02/2024, 08:55

Talk

Unraveling the mysteries of Intrinsically Disordered Proteins (IDPs) and Regions (IDRs) is one of the greatest challenges in the 21st century. The flexibility of these regions allow proteins to adopt vastly different conformations, allowing them to facilitate the binding and unbinding of vital activation sites. These regions, even in well-studied proteins such as the tumor...

30. Integrative Biology to tackle mitochondrial respiration in Alzheimer’s pathogenesis

Montserrat Soler Lopez (ESRF)

14/02/2024, 09:20

Talk

Respiratory complexes located in the internal membranes of our mitochondria are true macromolecular batteries: they couple the flow of electrons through clusters of metals and cofactors with a transfer of protons to create a gradient that provides the energy necessary for the ATP production and therefore to the nourishment of essential life processes. The first complex in the respiratory...

56. NMR Provides Unique Insight into the Functional Dynamics and Interactions of Intrinsically Disordered Proteins involved in Viral Replication

martin blackledge

14/02/2024, 10:15

Talk

Proteins are inherently dynamic, exhibiting conformational freedom on many timescales,[1] implicating structural rearrangements that play a major role in molecular interaction, thermodynamic stability and biological function. Intrinsically disordered proteins (IDPs) represent extreme examples where flexibility defines molecular function. In spite of the ubiquitous presence of IDPs throughout...

41. Structure and function relationships in protein homorepeats

Pau BERNADO (Centre de Biologie Structural (CBS-Montpellier))

14/02/2024, 10:40

Talk

Homorepeats, repetitive sequences inserted in disordered proteins, play fundamental roles in biology and mutations in these low-complexity regions are linked to several neurodegenerative and developmental diseases. Despite their relevance, the structural characterization and modelling of these proteins remain challenging. From an experimental perspective, the severe signal overlap of their NMR...

38. Integrative structural biology with atomic force microscopy data

Jean-Luc Pellequer (IBS)

14/02/2024, 11:05

Talk

Understanding the molecular and cellular function of biological molecules requires an accurate perception of their functional assemblies. The term "functional" refers to the actual structure of the bioactive molecule: it includes, but is not limited to, oligomerization, molecular partners, and their multiscale dynamics. Achieving such a functional goal requires a combination of techniques that...