REFLEX: RNA Ensemble Generation via Flexibility-Calibrated Stochastic Bridge

RNA molecules often function through multiple experimentally observed conformational states. A central challenge is to capture ensemble diversity without sacrificing structural fidelity: samples may collapse toward averaged representative structures or drift into unsupported conformational regions. We introduce $\text{REFLEX}$ (RNA Ensemble generation calibrated by FLEXibility), a sequence-conditioned generator for RNA backbone-frame ensembles based on a heteroscedastic stochastic bridge on $\mathrm{SE}(3)$. During training, experimental $\mathrm{B}$-factors calibrate residue-wise bridge widths, exposing each observed conformer through local perturbation neighborhoods with residue-specific scales while keeping constrained regions sharper. A learned flexibility condition guides the bridge-field network to recover target conformer-specific frames from these calibrated noisy states. At inference, $\text{REFLEX}$ uses only the input sequence, requiring no MSA-subsampling heuristics. On held-out multi-conformer RNA clusters, $\text{REFLEX}$ achieves the best precision–recall trade-off for ensemble coverage across evaluation thresholds, while ablations indicate that the learned bridge field recovers conformer-specific basins more reliably.