Transition model for ricin-aptamer interactions with multiple pathways and energy barriers

Area of Science:

• Biophysics
• Molecular Biology
• Biochemistry

Background:

• Single-molecule interactions are crucial for biological processes.
• Understanding unbinding pathways is key to characterizing molecular binding dynamics.
• Ricin-aptamer interactions serve as a model system for studying complex binding events.

Purpose of the Study:

• To develop a transition model for interpreting single-molecule ricin-aptamer interactions.
• To elucidate multiple unbinding pathways and energy barriers.
• To analyze the influence of loading rates on unbinding event redistribution.

Main Methods:

• Atomic force microscopy dynamic force spectroscopy (AFM-DFS) was employed to measure unbinding forces.
• Molecular dynamics simulations were used to correlate binding conformations with unbinding pathways.
• Markov-type transition matrices were developed to model event redistribution.

Main Results:

• Single-molecule ricin-aptamer unbinding follows multiple pathways, each characterized by distinct energy barriers.
• A direct relationship was established between binding conformations and specific unbinding pathways.
• The redistribution of unbinding events across pathways is dependent on applied loading rates.

Conclusions:

• The developed transition model accurately interprets complex ricin-aptamer unbinding dynamics.
• The findings provide a detailed understanding of multi-pathway unbinding mechanisms.
• This work offers a framework for analyzing similar complex molecular interactions.