Ensemble Lens: Comparing Conformational Ensembles to Explain How Two Drug Candidates Reshape Aβ42

Authors

Augustine Nwafor (Louisiana State University), Eric First (Louisiana State University of Health Sciences), Urska Cvek (LSU Shreveport)

Abstract

Adaptive molecular dynamics generates thousands of short, unequal trajectories labeled by abstract Markov state identifiers, yet the scientific question is whether a drug candidate alters the conformational ensemble of a disordered peptide. We present Ensemble Lens, an interactive comparative visualization in which every view places the three simulated systems side by side on shared scales, enabling readers to interpret abstract state labels as shapes, interactions, and mechanisms. Two principles guide the design: encoding measurements relative to a reference system and subtracting an explicit chance-contact baseline before attributing any interaction to binding. Applied to the CoVAMPnet Aβ42 dataset, the visualization reveals differences between tramiprosate and its metabolite SPA that are obscured by state populations alone.