RNAtive to recognize native-like structure in a set of RNA 3D models

Motivation: Most widely used methods for evaluating RNA 3D structure models depend on the availability of experimental reference structures, which restricts their use for novel RNAs. Moreover, they often overlook recurrent structural features shared across multiple predictions of the same sequence. Although consensus approaches have proven effective in RNA sequence analysis and evolutionary studies, no existing tool applies these principles to evaluate ensembles of 3D models. This gap hampers the identification of native-like folds in computational predictions, particularly as AI-driven methods become increasingly prevalent. Results: This paper presents RNAtive, the first computational tool to apply consensus-derived secondary structures for reference-free evaluation of RNA 3D models. It aggregates recurrent base-pairing and stacking interactions across ensembles of predicted 3D structures to construct a consensus secondary structure. Models are then ranked using two metrics derived from binary classification. Benchmark results show that models aligning with the consensus tend to exhibit native-like structural features, as validated against experimental data from CASP15. The RNAtive web server offers an intuitive platform for comparing and prioritizing RNA 3D predictions, providing a scalable solution to address the variability inherent in deep learning and fragment-assembly methods. By bridging consensus principles with 3D structural analysis, RNAtive advances the exploration of RNA conformational landscapes and has potential applications in fields like therapeutic RNA design. Availability: RNAtive is a freely accessible web server with a modern, user-friendly interface, available for scientific, educational, and commercial use at https://rnative.cs.put.poznan.pl/.