Cell dynamics of folding in two-dimensional model proteins

Area of Science:

• Computational biophysics
• Protein folding dynamics

Background:

• Proteins must fold into native states for function.
• Rapid folding is linked to restricted conformational exploration (folding funnels).
• Lattice models offer controlled environments for studying folding kinetics.

Purpose of the Study:

• Design rapidly folding protein sequences.
• Investigate folding dynamics in a simplified model.
• Characterize folding funnels using coarse-grained methods.

Main Methods:

• Developed a 2D heteropolymer lattice model.
• Assigned strong couplings to native state contacts.
• Analyzed folding transition and glass transition temperatures.
• Studied median folding times and temperature dependence.
• Mapped dynamics using cell dynamics and maximally compact cells.

Main Results:

• Designed sequences with high folding transition temperatures.
• Observed low glass transition temperatures in designed sequences.
• Demonstrated temperature-dependent folding times.
• Illustrated folding pathways via cell dynamics.

Conclusions:

• Folding funnels can be operationally defined.
• Mapping states to compact conformations reveals connectivities.
• Provides a coarse-grained approach to understanding folding funnels.