Quantifying the kinetic paths of flexible biomolecular recognition

Area of Science:

• Biophysics
• Computational Biology
• Biochemistry

Background:

• Biomolecular recognition frequently involves significant conformational changes, including local unfolding.
• Understanding the kinetic pathways of these binding-folding processes is crucial for elucidating molecular interactions.

Purpose of the Study:

• To develop a novel path-integral framework for studying the dynamics of biomolecular binding-folding processes.
• To determine and quantify dominant kinetic pathways and their correlation with molecular folding.

Main Methods:

• Establishment of a path-integral framework on the energy landscape.
• Quantification of dominant kinetic paths for binding and folding.
• Analysis of the coupling effects between binding and folding dynamics.

Main Results:

• Identified dominant kinetic paths for binding and folding, showing strong correlation when coupling is significant.
• Demonstrated that binding and folding can occur concurrently due to cooperative dynamics.
• Observed a bell-shaped temperature dependence for the kinetic rate in the concentration-saturated regime.

Conclusions:

• The proposed framework effectively models the coupled binding-folding dynamics of biomolecules.
• The interplay between binding and folding significantly dictates the overall kinetic process and rate.
• The findings provide insights into the mechanisms underlying biomolecular recognition and function.