Exploring the balance between folding and functional dynamics in proteins and RNA

Area of Science:

• Computational Biology
• Biophysics
• Structural Biology

Background:

• Biomolecules transition between ordered and disordered states during function.
• Studying these dynamics computationally is challenging due to large molecule sizes and long timescales.
• Simplified models are needed to reduce computational demand while retaining accuracy.

Purpose of the Study:

• To explore a class of simplified models for biomolecular dynamics.
• To assess the models' ability to capture structural fluctuations and stability.
• To provide a foundation for studying disorder in ribonucleoprotein (RNP) assemblies.

Main Methods:

• Explicitly representing all non-hydrogen atoms in a simplified model.
• Testing the model on representative biomolecules, including tRNA and ribosomes.
• Analyzing protein folding, native-basin dynamics, and structural fluctuations.

Main Results:

• The simplified model consistently describes protein folding and native-basin dynamics.
• Native-basin fluctuations of tRNA and ribosomes are robust to model variations.
• The extended variable loop in tRNAIle is predicted to be highly dynamic.

Conclusions:

• Simplified models can accurately represent large-scale biomolecular dynamics.
• This approach is suitable for studying transient disorder in functional biomolecules.
• The findings support the application of simplified models to RNP assemblies.