Sequence-dependent shape and stiffness of DNA and RNA double helices: hexanucleotide scale and beyond

Abstract

The structure and deformability of double-stranded DNA and RNA depend on the sequence of bases, affecting biological processes and nanostructure design. Despite intense research, the dependence is incompletely understood. Here we present mechanical properties of DNA and RNA duplexes inferred from atomic-resolution, explicit-solvent molecular dynamics (MD) simulations of 107 DNA and 107 RNA oligomers containing all hexanucleotide sequences. The sequence-specific parameters include structure and stiffness at the rigid base level, the width and stiffness of major and minor grooves, and global material constants such as stretch modulus, twist rigidity, or bending and twisting persistence lengths. We propose a simple model to predict sequence-dependent shape and harmonic stiffness for arbitrary sequence, validate it on an independent set of MD simulations for DNA and RNA duplexes containing all pentamers, and demonstrate its utility in various applications. The large amount of simulated data enabled us to study rare events, such as base-pair opening lifetimes, or flips of the RNA sugar pucker into the B domain and the related dynamics of the 2-OH group. Together, this work provides a comprehensive sequence-specific description of DNA and RNA duplex mechanics, forming a baseline for further research and allowing for a broad range of applications.