• Architecture of the ribosome RNA-protein machine assembly
• 49 min
  1. High resolution structure of ribosomal subunits RNA/RNA and protein/RNA interactions

  • Prof. Nenad Ban
• 38 min
  2. Assembly of the 30S ribosomal subunit in vitro and in cells

  • Prof. James Williamson
• Decoding and peptide bond formation
• 46 min
  3. How aminoacyl-tRNA synthetases translate the genetic code

  • Dr. Stephen Cusack
• 42 min
  4. The structural basis for how the large ribosomal subunit catalyses peptide bond formation

  • Prof. Thomas Steitz
• 47 min
  5. Elongation of protein synthesis: structural basis of the process of decoding

  • Prof. Marina Rodnina
• Initiation of protein synthesis
• 49 min
  6. The structure-based mechanism of translation initiation in bacteria and eukaryotes

  • Prof. Jeffrey Kieft
• 48 min
  7. Factor independent initiation of protein synthesis by IRES RNAs

  • Prof. Jeffrey Kieft
• Elongation and termination of protein synthesis
• 41 min
  8. Translocation: movement of tRNA and mRNA through the ribosome

  • Prof. Harry Noller
• 31 min
  9. Recoding: getting more out of the message by shifting reading frame and redefining codon meaning

  • Prof. John Atkins
  • Prof. Raymond Gesteland
• Co-translational protein secretion
• 75 min
  10. Mechanism of translocon function: current insights and models

  • Prof. Arnold Driessen
• How antibiotics target the ribosome
• 29 min
  11. Antibiotics that target the 50S ribosome subunit: resistance and other considerations

  • Dr. Joyce Sutcliffe
• 35 min
  12. Antibiotic inhibition of ribosome function

  • Dr. Daniel Wilson
• 45 min
  13. Structure-based drug design targeting infectious disease

  • Dr. Erin Duffy
• Archived Lectures *These may not cover the latest advances in the field
• 26 min
  14. Structural insights into aminoacyl-tRNA delivery by EF-Tu and translocation by EF-G

  • Prof. Joachim Frank
• 21 min
  15. Introduction to the ribosome

  • Prof. Anders Liljas
• 20 min
  16. The structure of the intact ribosome and ribosomal subunit interactions

  • Dr. Jamie H. Doudna Cate
• 42 min
  17. Structural insights into decoding of mRNA by the ribosome

  • Prof. Venki Ramakrishnan
• 63 min
  18. Chemistry of peptide bond formation

  • Prof. Rachel Green
• 49 min
  19. The interaction of antibiotics with the large ribosomal subunit from Haloarcula marismortui

  • Prof. Peter Moore

Printable Handouts

PDF

Navigable Slide Index

1. Introduction
2. Many antibiotics inhibit the ribosome
3. Intelligent engine builds perpetual pipeline (1)
4. Crystallography shows 50s is a target-of-targets
5. From new X-ray crystals to new leads
6. AnalogTM
7. LINKER essentials: tethering two binding features
8. BOMB essentials: grow
9. BOMB essentials: grow, search
10. BOMB essentials: score, refine
11. MUSIC essentials: core-swapping
12. QikProp - calculating drug-like properties
13. Structures + AnalogTM: balanced compounds
14. Case study: enhanced oxazolidinones
15. Structural foundations
16. Path to enhanced oxazolidinones
17. Py contributions represent key interactions
18. Probing selectivity of sparsomycin
19. Seeking a new lead
20. The results (1)
21. Difference density map showing rib-X prototype
22. Modeling - a perfect match
23. The results (2)
24. A minimal scaffold for lead optimization
25. Minimal scaffold binds effectively in A-site
26. Activity against H. influenzae
27. H. influenzae activity with time evolution
28. H. flu model delivers differentiable oxazolidinones
29. Moderate in vivo activity measured
30. Predictive model for rat oral bioavailability
31. First pool of drug candidates
32. Structures + predictive models = time-saving filters
33. Intelligent engine builds perpetual pipeline (2)
34. Acknowledgments

Topics Covered

• Many antibiotics inhibit the ribosome
• Intelligent engine builds perpetual pipeline
• Crystallography shows 50S is a target-of-targets
• From new X-ray crystals to new leads
• Analog(Trade Mark)
• LINKER essentials: tethering two binding features
• BOMB essentials
• MUSIC essentials: core-swapping
• QikProp: calculating drug-like properties
• Structures + Analog(Trade Mark): balanced compounds
• Case study: enhanced oxazolidinones
• Structural foundations
• Path to enhanced oxazolidinones
• Pi contributions represent key interactions
• Probing selectivity of sparsomycin
• Seeking a new lead
• Difference density map showing rib-X prototype
• Perfect match
• A minimal scaffold for lead optimization
• Minimal scaffold binds effectively in A-site
• Activity against H. influenzae
• H. influenzae activity with time evolution
• H. flu model delivers differentiable oxazolidinones
• Moderate in vivo activity measured
• Predictive model for rat oral bioavailability
• First pool of drug candidates
• Structures + predictive models = time-saving filters

Links

Series:

• The Mechanisms of Ribosome Function

Categories:

• Biochemistry
• Microbiology
• Pharmaceutical Sciences

Therapeutic Areas:

• Infectious Diseases

Talk Citation

Publication History

• Published on May 15, 2008

Financial Disclosures

• Dr. Erin Duffy has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.