The Gō model revisited: Native structure and the geometric coupling between local and long-range contacts

Area of Science:

• Computational physics
• Biophysics
• Polymer science

Background:

• Understanding protein folding kinetics is crucial for molecular biology.
• Lattice polymer models provide simplified yet insightful frameworks for studying folding dynamics.
• The role of specific interactions, like long-range forces, in folding pathways requires detailed investigation.

Purpose of the Study:

• To investigate the impact of long-range interactions on the folding rates of 48-mer lattice polymers using Monte Carlo simulations.
• To analyze how different native geometries and the strength of long-range interactions affect polymer folding times.
• To explore the relationship between geometric coupling, local contacts, and long-range interactions in determining folding kinetics.

Main Methods:

• Monte Carlo simulations were employed to model 48-mer three-dimensional lattice polymers.
• The Gō potential was used to represent interactions, with varying contributions from long-range forces.
• Folding times were simulated for three distinct target native structures.

Main Results:

• A sharp increase in folding time was observed as the contribution of long-range interactions decreased from 50% to zero.
• Folding time dispersion varied significantly across different native geometries, spanning three orders of magnitude.
• A strong geometric coupling between local and long-range contacts was identified in some target structures, facilitating folding.
• Absence of strong geometric coupling led to increased sensitivity to energy parameters and longer folding times.

Conclusions:

• Long-range interactions are critical determinants of polymer folding rates.
• Native geometry plays a key role in modulating the influence of long-range interactions and the dispersion of folding times.
• Geometric coupling between local and long-range contacts significantly impacts folding pathways and efficiency.