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FORGE audits residue-level information encoded in RNA tertiary-structure geometry

Sep 2026 · bioRxiv · 0 citations · 15 references
Biology

Abstract

Coarse RNA coordinate representations are widely used, yet the biological information they encode remains unquantified. We introduce FORGE, which converts a seven-atom RNA geometry representation into 935 interpretable descriptors and reports which residue-level annotations this geometry supports. On 4,135 post-2025 RNA chains, FORGE recovered 64.6% of native nucleotides; a six-atom control lacking the glycosidic nitrogen retained 58.5%, locating most of this signal in phosphate–sugar geometry. Confidence was sharply graded: abstaining from the least-confident half of positions raised accuracy to 94.4%, yet many chains remained only partially identifiable. The same descriptors predicted base-pair state far better than a DMS-like proxy or protein-proximal context. Native–decoy, OpenKnot and solved-pseudoknot analyses showed that nucleotide identifiability, foldability and experimental design score are separable: AlphaFold 3 reproduced the experimental fold for one of four AI-designed constructs and none of the sequences FORGE read from their geometry. FORGE provides a reproducible audit layer for RNA structural interpretation.

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