Keynote talk at RNA Club 2023 in Olšina, Czechia.

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Exploring ribosome dynamics through large-scale computer simulations

Michal H. Kolář

michal@mhko.science

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Computer simulations may provide atomistic details of ribosome structure, dynamics, and energetics.

    1. ribosome essentials

    2. molecular dynamics simulations

    3. co-translational folding of VemP

    4. long-range allostery

    5. ongoing studies

    1. ribosome essentials

    2. molecular dynamics simulations

    3. co-translational folding of VemP

    4. long-range allostery

    5. ongoing studies

    1. ribosome essentials

    2. molecular dynamics simulations

    3. co-translational folding of VemP

    4. long-range allostery

    5. ongoing studies

„Prediction is very difficult, especially if it’s about the future.“

foto AB Lagrelius & Westphal

MD simulations forecast molecular events based on laws of physics.

Generated by AI 2023-10-22, bing.com: "predicting future based on laws of physics, cartoon, black-white style enhanced by shades of blue"

  • averages (structure)
  • fluctuations (dynamics)
  • thermodynamics (ΔG, ΔS, KD)
  • rates of processes (lifetimes, rate constants)
  • biophysical data (NMR, SAXS)

Three challenges related to the ribosome

foto: Mikael Kanerva link

2500+1500 nodes
0.55 exaFLOP
€ 144 million

foto: Fade Creative link

    1. ribosome essentials

    2. molecular dynamics simulations

    3. co-translational folding of VemP

    4. long-range allostery

    5. ongoing studies

Bock et al. PMID: 29202442
Kolář et al. PMID: 35150281



Helmut Grubmüller
Lars V. Bock
Gabor Nagy

Sara M. Vaiana
John Kunkel

Vibrio alginolyticus

Vibrio Export Monitoring Polypeptide (VemP)

 

photo courtesy: Dr. Gary Gaugler, Visuals Unlimited, Inc.
Ishii et al., PMID: 26392525

VemP

  • cryo-EM shows extreme compation in the exit tunnel
  • Su et al., PMID: 28556777

 

  • inner helix inactivates two nucleobases needed for peptidyl transfer

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The tunnel walls play a decisive role in folding VemP.

Structure

Dynamics

    1. ribosome essentials

    2. molecular dynamics simulations

    3. co-translational folding of VemP

    4. long-range allostery

    5. ongoing studies

McGrath et al. PMID: 29202442

 

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The presence or absence of PDF can be predicted from conformations of distant ribosome parts.

Prediction accuracy

    1. molecular dynamics simulations

    2. ribosome essentials

    3. co-translational folding of VemP

    4. long-range allostery

    5. ongoing studies

Coarse-grained simulations

Lower resolution, lower accuracy, larger timescales

Decoding of non-standard genetic code

with M. Eliáš group (University of Ostrava)

The stop-to-sense re-assignment can be explained by sequence divergence of the flagellate's release factor.

Ancestral ribosomes

with K. Hlouchová group (Charles University)

The peptides stabilize ancestral rRNA and help rRNA aggregation.

take this home:

Computer simulations may provide atomistic details of ribosome structure, dynamics, and energetics.

Exploring ribosome dynamics through large-scale computer simulations

Michal H. Kolář

michal@mhko.science

Structural analysis