Effect of surface binding on heterogeneous DNA melting equilibria: a Monte Carlo simulation study

Area of Science:

• Biochemistry
• Molecular Biology
• Computational Chemistry

Background:

• DNA microarrays rely on specific probe-target hybridization for detection.
• Surface immobilization of DNA probes is crucial for microarray function.
• The hybridization equilibrium of surface-bound DNA is not fully understood.

Purpose of the Study:

• To investigate the effect of surface binding on DNA hybridization equilibrium.
• To determine how surface immobilization influences the dissociation of DNA duplexes.
• To explore the impact of different binding orientations on DNA stability.

Main Methods:

• Configurational-bias Monte Carlo simulations were employed.
• A coarse-grained model for deoxyribonucleic acid (DNA) was utilized.
• Simulations were performed for an undecamer DNA double helix in solution and on a surface.

Main Results:

• Surface binding was found to shift the hybridization equilibrium.
• Hydrogen-bonding interactions of proximal bases were destabilized by surface binding.
• Hydrogen-bonding interactions of distal bases were enhanced when the DNA lay flat on the surface.
• Four distinct surface binding orientations were analyzed.

Conclusions:

• Surface immobilization significantly impacts DNA hybridization thermodynamics.
• The orientation of DNA on a surface influences binding stability.
• These findings are critical for accurate prediction of surface-bound DNA hybridization equilibria.
• Implications exist for the design and optimization of DNA-based technologies.