Advanced coarse-grained model for fast simulation of nascent polypeptide chain dynamics within the ribosome

Area of Science:

• Molecular Biology
• Computational Biophysics
• Structural Biology

Background:

• The nascent polypeptide exit tunnel (NPET) within the ribosome is crucial for protein folding and function.
• Simulating dynamics within the NPET is challenging due to the ribosome's size and the timescale of protein elongation.

Purpose of the Study:

• To develop an automated pipeline for creating a coarse-grained (CG) bead model of the NPET and ribosome surface.
• To enable computationally feasible simulations of co- and post-translational processes within the NPET.

Main Methods:

• Automated extraction of high-resolution NPET and ribosome surface geometry from structural data.
• Conversion of extracted geometry into a coarse-grained (CG) bead model suitable for molecular simulations.
• Application of the CG model to simulate nascent polypeptide elongation and escape dynamics.

Main Results:

• The developed CG model provides a more accurate representation of NPET geometry compared to previous models.
• The CG model facilitates simulations of nascent polypeptide elongation and post-translational escape.
• The model allows for the evaluation of free energy landscapes and electrostatic influences on polypeptide escape.

Conclusions:

• The new CG model significantly advances the simulation capabilities for studying protein translation dynamics within the NPET.
• This approach overcomes computational limitations of all-atom methods for simulating complex co- and post-translational events.
• The model serves as a valuable tool for investigating the intricate mechanisms of protein folding and maturation within the ribosome.