Modelling Macromolecular Machines

Molecular machines are nanoscale assemblies performing specific functions for an organism. Living cells build thousands of custom-designed macromolecular complexes such as the ribosome, transcriptional machinery, motors and transporters, all of which work in a precisely organized manner. With the advances in the structural biology methods modelling of such large systems has recently become possible. The lecture covers the modelling techniques currently developed and applied in the studies of macromolecular complexes, such as ribosomes, viruses, chromatin, RNA polymerases and molecular motors.

Program:

  • Overview of macromolecular machines and motors (basics of translation, structure of the ribosome, RNA polymerase, nucleosome, ATP synthase)
  • Low-resolution models for biomolecules (coarse-grained force fields for proteins and nucleic acids - Elastic Network Models, Go models, one-bead models, multiple-bead models)
  • Simulations of internal dynamics and its analysis techniques (molecular and Langevin dynamics, normal mode analysis, principal components analysis, fluctuations, correlations)
  • Collective motions of the ribosome explored with crystallography, cryo-electron microscopy, molecular dynamics, and normal mode analysis
  • Electrostatics of bionanosystems (Poisson-Boltzmann model and beyond)
  • Viruses (swelling of viral capsids, internal motions of HIV-1 protease)
  • Inhibitors of protein synthesis (binding of antibiotics to the ribosome, improving known antibiotics)
  • Self-assembly of macromolecules (assembly of the ribosomal subunits: experimental and theoretical approaches)
  • Brownian dynamics: investigating biomolecular association and kinetics of binding
  • Modelling of chromatin fibers and nucleosome
  • Modelling macromolecular crowding (effects of crowding on protein folding and stability, kinetics, and internal motions)
  • Overview of biomolecular modelling packages

Lecture Notes