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Mechanism of Ribosomal Antibiotics-Induced Stalling Studied by Molecular Dynamics Simulations and Non-Equilibrium Statistical Physics

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  • Full or part time
    Prof Helmut Grubmuller
  • Application Deadline
    Applications accepted all year round

Project Description

- You are a physicist or chemist who wants to reveal how life works at the molecular level?
- You know how to combine computer power and theory to solve biological problems?
- You just love doing science?
> You are most welcome!

The ribosome synthesizes proteins by catalyzing peptide bonds between amino acids and is the target for many antibiotics. The growing peptide chain leaves the ribosome through a 10 nm exit tunnel. Certain antibiotics, the macrolides, bind inside this tunnel. Depending on the sequence of the peptide, the presence of these antibiotics can have different consequences: (1) peptides are not able to pass by the antibiotic, thereby stalling the ribosome, (2) peptides extend further than the antibiotic binding site but are stalled at a later stage, and (3) peptides can pass the antibiotic and become fully synthesized. This sequence-specific stalling is used by bacteria as a sensor for the presence of the antibiotics and to regulate resistance mechanisms, but also has pharmacological implications. The aim of the project is to use extensive MD simulations of different peptides and antibiotics in the ribosomal tunnel to understand how the interplay between the peptides, the antibiotics and the ribosome leads to the sequence-specific stalling, and to rationalize the results in terms of a simplified statistical mechanics model. (paper: https://www.nature.com/articles/ncomms12026)

The successful candidate has a keen interest in computational molecular biophysics and in interdisciplinary collaborative research, as well as a strong background in theoretical physics or physical chemistry, structural biology, and scientific computing. Candidates hold (or expect to complete soon) a Master’s or equivalent degree in any of these or a related field.

The group language is English, so no German language skills are required – but it’s a great opportunity for you to learn German!

The Max Planck Society is committed to increasing the number of individuals with disabilities in its workforce and therefore encourages applications from such qualified individuals.

Interested? Submit your application including cover letter (explaining background and motivation), CV, transcripts, and publication record preferably via e-mail as one single PDF file to [Email Address Removed]

Funding Notes

The student will have the opportunity to participate in one of several available PhD programs, with three years funding and a possibility of extension, in collaboration with the University of Göttingen. Masters students aiming at a fast track PhD are also welcome.
Payment and benefits are based on the TVöD guidelines. The starting date is flexible.

References

A combined cryo-EM and molecular dynamics approach reveals the mechanism of ErmBL-mediated translation arrest, Stefan Arenz, Lars V. Bock, Michael Graf, C. Axel Innis, Roland Beckmann, Helmut Grubmüller, Andrea C. Vaiana & Daniel N. Wilson, Nature Communications volume 7, Article number: 12026 (2016), https://www.nature.com/articles/ncomms12026



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