The team will develop a Dynamic Ensemble-to-Rescue (DETR) generalizable platform to predict IDR behavior from sequence, identify transient disease-relevant conformational states, and design interventions that block pathological conformations and restore protein function. DETR will predict whether an IDR will fold into dysfunctional shapes, aggregate, or differentially interact with molecules that help complete critical functions under different conditions; identify protein shapes for diagnostic and therapeutic applications; and design protein and cyclic peptide binders for Parkinson’s disease and other synucleinopathies (neurodegenerative disorders caused by the abnormal buildup and misfolding of alpha-synuclein protein aggregates in the nervous system) and rare Ewing sarcoma as initial clinical indications.