Protein folding: from theory to practice.

Area of Science:

• Computational Biology
• Biophysics
• Protein Dynamics

Background:

• Direct comparison between experimental protein folding studies and theoretical models is challenging due to differing control parameters (e.g., denaturants/force vs. temperature).
• Existing theoretical frameworks often struggle to replicate experimental conditions, limiting predictive power in protein folding research.

Purpose of the Study:

• To introduce and validate the molecular transfer model (MTM) for simulating protein folding under experimentally relevant conditions.
• To enable direct, quantitative comparisons between theoretical predictions and laboratory findings in protein folding thermodynamics and kinetics.

Main Methods:

• Developed the molecular transfer model (MTM) to incorporate environmental changes into molecular simulations using measured quantities.
• Performed all-atom simulations to investigate protein folding pathways and intermediate states, including dry globules.

Main Results:

• MTM simulations demonstrated remarkable agreement with experimental data for protein folding thermodynamics and kinetics across multiple proteins.
• Simulations provided evidence for the existence of dry globules as potential intermediates in the protein folding process.

Conclusions:

• The molecular transfer model (MTM) successfully reconciles theoretical simulations with experimental protein folding studies.
• MTM and all-atom simulations represent significant advancements, offering new insights into protein folding mechanisms and the role of dry globules.