ScanFold

ScanFold identifies and maps potentially functional RNA secondary structures within individual viral RNA sequences by scanning for regions with unusually negative thermodynamic z-scores to prioritize structure–function candidates.

Key Features:

• Single-Sequence Analysis: Operates on individual RNA sequences without requiring curated sequence alignments or evidence of structural conservation.
• Thermodynamic Z-Scores: Scans input RNA sequences to compute thermodynamic z-scores and highlights regions with unusually negative values indicative of stable secondary structures.
• Base Pair Identification: Pinpoints specific base pairs that contribute to identified stable structures for further analysis.
• Integration with Experimental Data: Predictions have been compared with SHAPE reactivities and higher base pairing probabilities and applied to viral genomes including ZIKV (Zika virus) and HIV-1 (Human Immunodeficiency Virus 1).

Scientific Applications:

• Viral RNA structural mapping: Enables virologists and molecular biologists to explore the structural landscape of viral RNAs and identify candidate functional motifs.
• Candidate prioritization for structure–function studies: Prioritizes regions for experimental validation and detailed structure–function analyses.
• Informing mechanistic and therapeutic studies: Provides structural hypotheses to support investigations of viral mechanisms and the development of targeted interventions.

Methodology:

ScanFold scans input RNA sequences, computes thermodynamic z-scores using folding energies and stability metrics, identifies windows with negative z-scores, and locates base pairs contributing to those stable structures while decoupling prediction from conservation analysis.