Single-molecule studies of flavivirus envelope dynamics: Experiment and computation

Area of Science:

• Virology
• Biophysics
• Structural Biology

Background:

• Flaviviruses display complex structural and functional variations.
• Traditional ensemble-averaging methods may overlook critical viral heterogeneities.
• Antiviral and gene therapy research has yielded moderate success.

Purpose of the Study:

• To review single-molecule fluorescence methods for investigating flaviviruses.
• To highlight the application of these methods to dengue virus.
• To discuss the synergy between single-molecule studies and molecular dynamics simulations.

Main Methods:

• Time-resolved Förster resonance energy transfer (trFRET) for envelope conformations.
• FRET-fluorescence correlation spectroscopy for intrinsic dynamics.
• Single particle tracking for cellular virus dynamics.
• Multiscale molecular dynamics (MD) simulations for near-atomic resolution.

Main Results:

• trFRET probes dengue envelope conformations.
• FRET-FCS investigates dengue envelope dynamics.
• Single particle tracking follows dengue virus cellular pathways.
• Advanced MD simulations provide near-atomic resolution of viral envelopes.

Conclusions:

• Single-molecule methods are crucial for understanding flavivirus heterogeneity.
• Combining fluorescence techniques with MD simulations enhances structural and dynamic insights.
• This integrated approach can elucidate flavivirus particle dynamics and infection processes.