Fast protein folding is governed by memory-dependent friction

Area of Science:

• Biophysics
• Computational Biology
• Protein Dynamics

Background:

• Protein folding rates are governed by free-energy barriers and friction.
• Evaluating friction directly is challenging, often relying on memoryless theories.
• Molecular dynamics simulations provide insights into protein folding mechanisms.

Purpose of the Study:

• To directly calculate time-dependent friction during protein folding.
• To assess the relative influence of friction versus free-energy barriers on folding rates.
• To investigate the impact of finite friction decay times on protein folding kinetics.

Main Methods:

• Utilized memory-kernel extraction methods based on the generalized Langevin equation (GLE) formalism.
• Calculated time-dependent friction for the fraction of native contacts reaction coordinate (Q).
• Analyzed data from molecular dynamics simulations of eight fast-folding proteins.

Main Results:

• Friction was found to be more influential than free-energy barriers in determining protein folding rates across diverse proteins.
• Proteins fold in a regime where finite friction decay times significantly reduce folding times.
• Observed reductions in folding times by up to a factor of 10 compared to memoryless friction predictions.

Conclusions:

• Direct calculation of time-dependent friction offers a more accurate understanding of protein folding dynamics.
• Friction's memory effects play a crucial role in accelerating protein folding.
• This work challenges assumptions of memoryless friction in protein folding rate theories.