Sequence-Dependent Shape and Stiffness of DNA and RNA Double Helices: Hexanucleotide Scale and Beyond

Area of Science:

• Biophysics
• Molecular Biology
• Materials Science

Background:

• The sequence-dependent mechanical properties of DNA and RNA are crucial for biological functions and nanostructure engineering.
• Current understanding of these sequence-structure-mechanics relationships remains incomplete.

Purpose of the Study:

• To comprehensively characterize the mechanical properties of DNA and RNA duplexes across all hexanucleotide sequences.
• To develop a predictive model for sequence-dependent nucleic acid mechanics.
• To investigate rare dynamic events in DNA and RNA duplexes.

Main Methods:

• Atomic-resolution, explicit-solvent molecular dynamics (MD) simulations of 107 DNA and 107 RNA oligomers.
• Analysis of global material constants including persistence lengths, stretching, and twisting rigidities.
• Development and validation of a predictive model using MD simulation data.

Main Results:

• Detailed sequence-specific mechanical properties (shape, stiffness) of DNA and RNA duplexes were elucidated.
• A validated model accurately predicts sequence-dependent mechanical behavior.
• Rare events like base-pair opening and A-RNA to B-DNA sugar pucker flips were observed and analyzed.

Conclusions:

• This work establishes a comprehensive, sequence-specific mechanical description of DNA and RNA duplexes.
• The developed model offers a powerful tool for predicting nucleic acid mechanics.
• Findings provide a foundational baseline for future research and diverse applications in biology and nanotechnology.