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TYC Highlight Seminar:Atomistic Simulation of Biomolecular Function: Ribosomal Translation, Ligand Binding Heterogeneity, and a Dynasome Perspective

Helmut Grubmüller - Professor, Director at the Max Planck Institute for Biophysical Chemistry

Friday 13th March 2020
Time: 4pm
Venue: Archaeology LT G6, followed by a reception in the Nyholm Room, Christopher Ingold Building
Contact: Karen Stoneham / Andela Saric
Tel: 0207 679 7306

Ribosomes are highly complex biological nanomachines which operate at many length and time scales. We combined single molecule, x-ray crystallographic, and cryo-EM data with atomistic simulations to elucidate how tRNA translocation and the action of antibiotics work at the molecular level. We describe a new combined allosteric mechanism for erythromycin-induced translational stalling of the antibiotics sensor peptide ErmB.  
Using streptavidin/biotin as a model system with super-strong affinity, we show that the underlying free energy landscape which governs ligand binding and unbinding
can be extracted from combined atomic force microscopy (AFM) and force probe simulation data, which covers loading rates of 11 orders of magnitude. We will, finally, take a more global view on the 'universe' of protein dynamics motion patterns and demonstrate that a systematic coverage of this 'Dynasome' allows one to predict protein function.

[1] Arenz S, Bock LV, ... , Grubmüller H, Vaiana AC, Wilson DN. Nature Comm. 7, 12026 (2016)
[2] Fischer N, ..., Stark H. Nature 540 (7631), 80-85 (2016) 
[3] Bock LV, Blau C, Vaiana AC, Grubmüller H. Nucl. Acids Res. 43 (14), 6747–6760 (2015)
[4] Bock LV, ..., Grubmüller H. Nature Struct. Molec. Biol. 20 (12), 1390-1396 (2013)
[5] Bock LV, Kolar MH, Grubmüller H.  Curr. Opin. Struct. Biol. 49, 27–35 (2018) 
[6] Huter P et al. Mol. Cell 68 (3), 515–527 (2017)
[7] Rico F, Russek A, Gonzalez L, Grubmüller H, Scheuring S. PNAS, 116 (14) 6594-6601 (2019)
[8] Hensen U, Meyer T, Haas J, Rex R, Vriend G, Grubmüller H.  PLoS One 7, e33931 (2012) 

Biography

Director, Theoretical and Computational Biophysics Department, Max Planck Institute for Biophysical Chemistry, Göttingen

Education and Scientific Career Study of Physics Technical University of Munich (1985), Diploma in Physics (1990); research visit at University of Illinois, Urbana-Champaign (1990/91); PhD Technical University of Munich (1994); visiting scientist CENG Grenoble, France (1994); postdoctoral fellow Ludwig-Maximilians University of Munich (1994–1998); EMBO Fellow ETH Zurich, Switzerland (1997); independent research group leader Max-Planck Institute for Biophysical Chemistry (1998–2003); German Habilitation & Venia Legendi in Physics, University of Göttingen (2002), Associate Professor, EPFL Lausanne Switzerland (2003); director and scientific member, Max-Planck Institute for Biophysical Chemistry (since 2003); honorary professor for Physics, University of Göttingen (since 2005); Rolf Sammet Laureate, Goethe University of Frankfurt/Main (2013)

Research interests

To achieve a 'first principles' understanding of the functional mechanisms of biomolecules and
bimolecular complexes through atomistic computer simulations, with a particular focus on proteins
and protein/RNA complexes such as the ribosome. Further, to advance simulation methods through progress in the theory of biomolecular dynamics and through improved scalable parallel algorithms.

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