A Coarse-Grained Model of Unstructured Single-Stranded DNA Derived from Atomistic Simulation and Single-Molecule...

Area of Science:

• Biophysics
• Computational Biology
• Molecular Modeling

Background:

• Accurate modeling of single-stranded DNA (ssDNA) is crucial for understanding its biological functions.
• Existing models may lack the balance between computational efficiency and biological accuracy.
• Experimental validation is key to confirming the reliability of computational models.

Purpose of the Study:

• To develop a simplified coarse-grained model for ssDNA.
• To ensure the model accurately reproduces ssDNA's structural and mechanical properties.
• To provide a computationally efficient tool for studying ssDNA and its interactions.

Main Methods:

• Developed a coarse-grained model with two sites per nucleotide (backbone and sugar/base).
• Utilized tabulated bonded potentials optimized against atomistic simulations for intra-nucleotide interactions.
• Employed isotropic potentials for nonbonded interactions, calibrated to match experimental ssDNA radius of gyration.
• Validated the model using force-extension measurements and Förster Resonance Energy Transfer (FRET) with optical tweezers.

Main Results:

• The model successfully reproduces the solution structure of ssDNA.
• It accurately predicts the force-extension relationship of ssDNA over two orders of magnitude of applied force.
• Experimental validation using FRET and optical tweezers confirmed the model's accuracy in predicting end-to-end distances.

Conclusions:

• The developed coarse-grained ssDNA model offers a balance of simplicity and accuracy.
• It provides a reliable computational tool for studying ssDNA behavior.
• The model's design allows for straightforward extension to more complex systems, including double-stranded DNA and protein interactions.