Localized potential well vs binding site: Mapping solute dynamics in a membrane channel onto one-dimensional...

Area of Science:

• Biophysics
• Computational Biology
• Physical Chemistry

Background:

• Solute molecule translocation through channels is crucial in biological processes.
• The interaction potential of mean force (U(x)) describes solute-channel wall interactions.
• Reversible binding can be modeled as a potential well or a discrete trapping site.

Purpose of the Study:

• To investigate the differences between potential well and discrete site models for solute binding in channels.
• To determine if translocation time distributions can distinguish between these binding mechanisms.
• To analyze the coefficient of variation of translocation times.

Main Methods:

• One-dimensional theoretical modeling of solute-channel interactions.
• Parameterization of potential well and discrete site models to match thermodynamic properties.
• Analysis of translocation probabilities, mean translocation times, and translocation time distributions.

Main Results:

• Both models yield identical equilibrium distributions, translocation probabilities, and mean translocation times when thermodynamically matched.
• Qualitatively different translocation time distributions are predicted: narrower for the potential well model, broader for the discrete site model.
• The coefficient of variation of translocation time is consistently <1 for the potential well model and can be >1 for the discrete site model.

Conclusions:

• Translocation time distribution analysis, beyond its mean, can differentiate between potential well and discrete site binding mechanisms.
• The coefficient of variation serves as a key metric to distinguish these models.
• Understanding these distinct mechanisms is vital for interpreting solute transport in biological channels.