Conformational dynamics of supramolecular protein assemblies

Area of Science:

• Structural biology
• Biophysics
• Computational biology

Background:

• Supramolecular protein assemblies are crucial for cellular functions.
• High-resolution structures are increasingly available via single-particle electron microscopy.
• Understanding protein dynamics is essential for inferring biological mechanisms.

Purpose of the Study:

• To present an unsupervised computational framework for analyzing the conformational dynamics of large protein assemblies.
• To apply this framework to structures in the Electron Microscopy Data Bank.
• To investigate thermal fluctuations, elastic strain energy, and dynamical correlations.

Main Methods:

• A coarse-grained modeling framework based on the finite element method.
• Analysis of equilibrium thermal fluctuations and elastic strain energy distributions.
• Computation of dynamical correlations between distant molecular domains.

Main Results:

• Identified hinge regions associated with specific conformational change pathways in protein assemblies.
• Revealed dynamical coupling between distant molecular domains, suggesting allosteric mechanisms.
• Applied the framework to the ribosome-bound termination factor RF2, nuclear pore complex, and chaperonin GroEL.

Conclusions:

• The computational framework provides insights into cooperative transitions and allosteric communication.
• The findings enhance understanding of molecular mechanics in protein assemblies.
• Results aid in the classification and refinement of electron microscopy-based structures.