Transition path dynamics in the binding of intrinsically disordered proteins: A simulation study.

Area of Science:

• Biophysics
• Polymer Physics
• Computational Chemistry

Background:

• Protein and biopolymer association is fundamental to biological processes.
• Single-molecule experiments provide detailed insights into association dynamics via transition paths.
• Developing accurate models is crucial for interpreting these experimental measurements.

Purpose of the Study:

• To develop models for understanding the dynamics of biopolymer association.
• To simulate the association dynamics of two oppositely charged, disordered polymers.
• To mimic experimental measurements using intermonomer distances as reaction coordinates.

Main Methods:

• Simulation study of association dynamics for two oppositely charged, disordered polymers.
• Monitoring intermonomer distances as experimental reaction coordinates.
• Applying generalized Langevin equation with a memory kernel to describe dynamics.

Main Results:

• Center-of-mass dynamics were memoryless and diffusive.
• Experimental reaction coordinates exhibited significant memory effects.
• Transition path time distribution was well-approximated by 1D diffusion with an apparent diffusion coefficient.
• Mean transition path time showed weak dependence on ionic strength despite electrostatic attraction.

Conclusions:

• The dynamics of biopolymer association can exhibit complex memory effects not captured by simple diffusive models.
• An apparent diffusion coefficient can effectively describe transition path dynamics in complex systems.
• Electrostatic interactions have a limited impact on the mean transition path time in this model system.