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Thermodynamic prediction of RNA cellular activity from sequence via conformational ensembles - PubMed

7 hours ago
  • #Thermodynamics
  • #RNA
  • #Conformational Ensembles
  • Thermodynamic prediction of RNA cellular activity from sequence via conformational ensembles.
  • Systematic alteration of HIV-1 TAR RNA sequence to change its propensity for functional vs. inactive secondary structure.
  • Quantification of active-state propensity using proton chemical exchange saturation transfer (1H CEST) NMR without isotopic labeling.
  • Minor sequence changes resulted in ~500-fold shifts in active-state propensity, predicting 125- to 300-fold changes in binding to Tat and cellular transactivation.
  • Secondary-structure prediction algorithms inferred propensities, incorporated into a thermodynamic framework for quantitative prediction of protein-binding affinity and cellular activity.
  • Established a quantitative thermodynamic framework linking RNA sequence to cellular activity through conformational ensembles.
  • Potential for generalized predictions as computational ensemble modeling advances.