SLIDE: Quantifying Transmembrane Protein Interface Specificity through Persistence Score and Friction Energy

Molecular dynamics simulations of transmembrane protein interfaces generate trajectories in which residue-residue contacts are continuously formed, broken, and reorganized. Existing analyses quantify contact occupancy but do not capture whether the same residue pairs remain associated or whether contact is maintained through continual exchange of partners. This work introduces SLIDE (Stability and Lability Interface Dynamics Evaluator), a framework that quantifies residue-pair turnover dynamics from unbiased trajectories. The Persistence Score measures turnover using Jaccard similarity between contact sets at different time lags, and friction energy E_friction quantifies the kinetic barrier against residue-pair rearrangement. Lipid-conditioned analysis computes ΔE_friction values quantifying how specific lipid species modulate interface dynamics, and Granger causality analysis distinguishes active lipid modulation from passive lipid recruitment. Validation using EGFR, Notch, and FGFR3 transmembrane domains demonstrates that specific interfaces and nonspecific associations are quantitatively distinguishable. SLIDE is freely available as an open-source Python package at https://github.com/takeshi-sato-dev/slide.