Invited seminar at Heyrovský Institute of Physical Chemistry, Czech Republic.

Created using Reveal.js.

Use right arrow for browsing.

Atomistic computer simulations of the ribosome

Michal H. Kolář

http://mhko.science/contact

http://mhko.science/jh-inst-2023

Helmut Grubmüller group


Marek Eliáš group

Klára Hlouchová group

1. Ribosome essentials

2. Atomistic simulations

3. Case study: PDF

1. Ribosome essentials

2. Atomistic simulations

3. Case study: PDF

1. Ribosome essentials

2. Atomistic simulations

3. Case study: PDF

Numerical integration of Newton's equations of motion using an empirical all-atom potential.

Three challenges

1. Atomistic simulations

2. Ribosome essentials

3. Case study: PDF

McGrath, Černeková, Kolář: PMID: 36335428

Strategy

  1. Build systems with and without PDF.
  2. Using MD simulations generate conformational ensembles.
  3. Search for differences in ribosome dynamics caused by PDF.

Technical details

  • Amber family of force fields
  • explicit SPC/E water, 150 mM KCl, 10 mM MgCl2
  • 2M particles
  • vsites for hydrogens, 4 fs time step
  • 1000 ns/traj, 4 independent trajs/system
  • Gromacs 2020, CPU-only implementation
  • 3.3M corehours
 

Structural analysis

take this home:

PDF affects the structure of the ribosomal protein uL22, simulations and experiment suggest.

Allostery via Principal Component Regression

Aim: Get a statistical model to predict F.

  1. Select atoms to test allostery.
  2. Cartesian coordinates ⟶ principle components (PCs).
  3. Dimensionality reduction (~100 PCs).
  4. Linear combination of selected PCs to correlate with F.
Hub, de Groot (2009): PMID: 19714202

Prediction accuracy

take this home:

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

Co-translational folding

How is a secondary structury of the nascent protein formed in the exit tunnel?

Decoding center of a eukaryotic organism

How does ribosome differentiate between various stop codons?

Protoribosome

What a prehistoric ribosome could look like?

Further reading

Bock, Gabrielli, Kolář, Grubmüller (2023): PMID: 36719969

Kolář, Nagy, Kunkel, Vaiana, Bock, Grubmüller (2022): PMID: 35150281

Bock, Kolář, Grubmüller (2018): PMID: 29202442

Kolář (2022): Kotranslační děje aneb první okamžiky života proteinu, Chemické listy

http://mhko.science/contact

http://mhko.science/jh-inst-2023