Conformational and environmental determinants of RNA solvation dynamics: roles of intrinsic flexibility, allostery, and protein binding

Solvation dynamics play a central role in shaping nucleic acid structure, flexibility, and recognition, yet their molecular origins remain poorly understood for RNA, whose diverse architectures and intrinsic conformational plasticity far exceed those of DNA. Here, we present the atomistic, microsecond-scale computational dissection of solvation dynamics in two structurally homologous but dynamically distinct viral RNAs-BIV TAR and HIV-2 TAR-in both apo and peptide-bound states, mimicking the salt concentration of the experimental time-resolved fluorescent spectroscopic measurements. By combining high-temporal-resolution solvation time correlation functions with detailed energy decomposition analyses, we uncover how water, ions, and RNA motions cooperatively shape relaxation across ultrafast to nanosecond timescales. Our results reveal that, unlike DNA, where slow components primarily reflect long-lived hydration and ion condensation, RNA can generate slow solvation decay either through long-lived hydration or through its own internal conformational fluctuations, such as involving spontaneous base-flipping events. Peptide binding modulates this conformational landscape in strikingly system-specific ways: BIV TAR RNA undergoes classical fluctuation quenching, where TAT binding suppresses RNA motions but shifts relaxation more toward solvent-RNA correlation, while HIV-2 TAR RNA exhibits a non-classical redistribution of solvent-ion-peptide correlations stemming from its weaker and more dynamic binding interface with TAT. The dominant slow decay in HIV-2 apo TAR maps directly onto an allosteric communication channel previously identified from structural analyses, demonstrating that solvation responses can sensitively report on RNA allostery. Together, this study bridges the experimental observations of time-resolved fluorescence spectroscopy with mechanistic molecular insights, establishes solvation dynamics as a powerful probe of RNA conformational energetics, and highlights how subtle differences in RNA-protein recognition can imprint distinct signatures on hydration and ion reorganization.