%0 Journal Article
%T RNA-Targeted Natural Product Discovery: Computational Rules for Molecular Recognition, Dynamics, Selectivity, and Validation
%A Lina Hassan
%A Omar Khalaf
%A Reem Jaber
%A Rania Mostafa
%J International Journal of Pharmaceutical And Phytopharmacological Research
%@ 2250-1029
%D 2026
%V 16
%N 2
%R 10.51847/Al0uS6OvXe
%P 164-173
%X RNA is increasingly tractable to small-molecule intervention, yet computational discovery still often inherits assumptions developed for protein targets: a comparatively stable receptor structure, transferable pocket definitions, simplified treatment of solvent and ions, and ranking by a single docking or affinity score. These assumptions are especially consequential for natural products, whose stereochemical density, ionizable functionality, conformational complexity, and frequent polypharmacology can amplify uncertainty in RNA recognition. This methodological article argues that RNA-targeted natural-product discovery requires a distinct computational grammar. The analysis integrates evidence on RNA-specific docking, electrostatics and solvation, conformational ensembles, motif recognition, RNA-binding chemical space, multi-conformation scoring, cellular selectivity, target engagement, functional modulation, and assay artefacts. The proposed framework treats receptor state, hydration and ion occupancy, motif context, ligand chemical-space priors, multi-conformation recognition, off-target RNA competition, and binding-to-function validation as coupled but non-substitutable decision layers. Natural-product origin is not treated as evidence of RNA selectivity; instead, natural products are considered chemically distinctive candidates whose behavior must be tested against alternative RNA states, competing nucleic acids, and assay liabilities. The framework does not establish universal scoring rules, prospective superiority over existing workflows, or translational readiness. Its purpose is to make uncertainty explicit and to define where computational prioritization should be challenged by orthogonal structural, biophysical, cellular, and functional evidence before an RNA-targeted natural product is advanced.
%U https://eijppr.com/article/rna-targeted-natural-product-discovery-computational-rules-for-molecular-recognition-dynamics-sel-qivcapxbf1elyxm