Cooperativity and contact order in protein folding

Area of Science:

• Computational biology
• Protein dynamics
• Biophysics

Background:

• Protein folding is a complex biophysical process crucial for protein function.
• Understanding the factors that govern protein folding kinetics is essential for molecular biology.
• Go-Lennard-Jones models provide a simplified framework for studying protein folding dynamics.

Purpose of the Study:

• To investigate the impact of cooperativity on protein folding kinetics within Go-Lennard-Jones models.
• To determine if cooperativity affects the kinetic universality classes of protein folding.
• To analyze the relationship between contact order, cooperativity, and folding times.

Main Methods:

• Utilized Go-Lennard-Jones models to simulate protein folding.
• Introduced cooperativity by making contact interactions dependent on proximity to the native conformation.
• Analyzed kinetic universality classes and folding times under varying degrees of cooperativity.
• Examined the role of contact order and its deviations in controlling folding scenarios.

Main Results:

• Kinetic universality classes remain unchanged in the presence of cooperativity.
• Small alterations in the effective contact map can significantly impact folding times, comparable to cooperativity effects.
• Contact order largely dictates folding scenarios, showing a monotonic dependence on sequential distances between amino acid pairs.
• Deviations from the contact order trend are the primary determinants of net folding times.

Conclusions:

• Cooperativity does not alter the fundamental kinetic universality classes of protein folding in these models.
• Folding times are primarily governed by the contact order and its deviations, with cooperativity playing a secondary role.
• The findings highlight the importance of contact order in predicting protein folding pathways and timescales.