FRETraj

FRETraj harmonizes single-molecule Förster resonance energy transfer (FRET) measurements with molecular dynamics simulations and de novo structure prediction for RNA and DNA.

Key Features:

• In silico FRET recreation: Recreates FRET experiments computationally using either all-atom or implicit fluorophore modeling.
• Structural dynamics visualization: Visualizes the underlying structural dynamics of nucleic acids and quantifies reaction coordinates.
• FRET-assisted ensemble filtering: Uses multiple accessible-contact volumes as a post hoc scoring method for fragment assembly in Rosetta to filter de novo RNA structure prediction ensembles by refuting models incompatible with in vitro FRET measurements.
• Computational fluorescence spectroscopy: Facilitates interpretability of dynamic structural ensembles and improves mechanistic understanding of nucleic acid interactions.

Scientific Applications:

• DNA structure validation: Benchmarks FRET-assisted modeling on double-labeled DNA strands.
• Dynamic riboswitch modeling: Validates the approach against an intrinsically dynamic manganese(II)-binding riboswitch.
• Four-way junction assembly: Uses a FRET coordinate describing four-way junction assembly to recapitulate the global fold of a riboswitch as displayed by crystal structure.

Methodology:

FRETraj uses all-atom or implicit fluorophore modeling to recreate FRET experiments in silico, and employs multiple accessible-contact volumes as a post hoc scoring method for fragment assembly in Rosetta.