Choosing Spatial Resolution in the Residence-Time Approach to Local Diffusivity

Abstract

Estimating position-dependent diffusivity with the residence-time approach (RTA) requires choosing an interval width that resolves spatial variation while probing time scales compatible with a local diffusion model. We develop a selection criterion that combines bulk diffusivity convergence with local model agreement measured by the Kullback-Leibler divergence between observed and predicted first-exit-time distributions, and assess global model agreement through independent propagator analysis against unbiased molecular dynamics. Applications to water in a fluid phospholipid bilayer and three permeants in a model skin lipid barrier show that local agreement alone does not ensure global fidelity: in the skin barrier, narrow intervals minimize exit-time mismatch but predict excessive spreading, whereas requiring bulk convergence selects wider intervals with better longer-time predictions. In propagator tests, RTA profiles at the selected interval widths outperform velocity-autocorrelation-based profiles and generally improve agreement relative to position-autocorrelation-based profiles in the skin barrier, while phospholipid-bilayer rankings depend on lag time and discrepancy metric; both autocorrelation methods use harmonically restrained simulations.