Mesoscopic model for DNA G-quadruplex unfolding

Area of Science:

• Biophysics
• Molecular Biology
• Genomics

Background:

• Guanine-rich sequences form G-quadruplexes, crucial for gene regulation and chromosome stability.
• Previous studies relied on computationally expensive all-atom simulations for G-quadruplex mechanical unfolding.

Purpose of the Study:

• To develop a mesoscopic model for simulating DNA G-quadruplex mechanical and thermal stability.
• To enable simulations at experimental loading rates, inaccessible to atomistic models.

Main Methods:

• A mesoscopic model representing nucleotides and central cations as single beads.
• Single-molecule force-induced unfolding experiments using high-resolution optical tweezers on a telomeric DNA sequence.

Main Results:

• The model successfully simulated DNA G-quadruplex unfolding at experimental loading rates.
• Model parameters fitted to experimental data accurately predicted rupture-force kinetics.
• Results showed good agreement with previous near-equilibrium measurements.

Conclusions:

• The mesoscopic model provides a powerful tool for studying G-quadruplex stability and dynamics.
• This approach offers a nanoscale paradigm for understanding non-equilibrium processes in biological systems.
• The model bridges the complexity gap between nucleic acid and protein structures.