Protein folding: matching theory and experiment

Area of Science:

• Biochemistry
• Physical Chemistry
• Computational Biology

Background:

• The interpretation of protein folding experimental results is influenced by folding funnels and simulations.
• The transition state model has evolved from a unique strained species to a more ordinary folding intermediate.

Purpose of the Study:

• To examine the impact of folding funnels and simulations on interpreting protein folding experimental results.
• To address the controversy surrounding populated folding intermediates: productive on-pathway or dead-end traps.

Main Methods:

• Analysis of experimental evidence regarding protein folding pathways.
• Review of theoretical models for protein folding intermediates.
• Examination of the role of alpha-helix formation in directing protein folding.

Main Results:

• Evidence suggests a broad transition barrier in protein folding, influenced by mutations.
• Little experimental evidence supports long-lived trapping in monomers, but good evidence exists for dimers.
• Fast alpha-helix formation significantly narrows folding routes, directing the folding process.

Conclusions:

• The current understanding of protein folding transition states has shifted.
• Distinguishing between productive and trapped folding intermediates requires direct experimental evidence.
• Alpha-helix formation acts as a key director in protein folding, altering the conceptual model from a funnel to a directed pathway.