Mapping a single-molecule folding process onto a topological space.

Area of Science:

• Polymer Physics
• Biophysics
• Computational Chemistry

Background:

• Protein folding physics traditionally uses nucleation-propagation and diffusion-collision models.
• Existing models do not fully account for chain topology during folding.
• Single-molecule techniques offer high-resolution real-time folding process monitoring.

Purpose of the Study:

• To map the complete topology landscape of a model polymeric chain.
• To investigate the role of topological properties in polymer folding dynamics.
• To bridge the gap between conceptual folding models and topological considerations.

Main Methods:

• Development and application of a novel circuit topology approach.
• Mimicking single-molecule mechanical interrogation by restraining chain ends.
• Monitoring fold nucleation dynamics and topological rearrangements.

Main Results:

• Transient local entropic loops precede nucleation.
• Nucleation length depends on cohesive interactions.
• Final topological states are primarily determined by folding speed, not interaction strength.
• Post-nucleation, transient topological rearrangements lead to a self-similar growth steady-state.

Conclusions:

• The circuit topology approach provides a comprehensive view of polymer folding landscapes.
• Folding speed is a critical determinant of a polymer chain's ultimate topological state.
• Understanding topological dynamics offers new insights into protein folding mechanisms.