DNA mechanics at the nanoscale: A computational perspective

Abstract

Double‐stranded DNA molecules are sharply bent into arcs with radii on the order of 10 nanometers in the formation of nucleosomes in biology and when they are looped into minicircles for nanoscale applications. In this Personal Account, we describe our computational efforts over the past several years to understand the structure and dynamics of sharply bent DNA using molecular dynamics simulations. First, using coarse‐grained models of DNA and cationic nanoparticles, we discuss how a small difference in sequence‐dependent DNA flexibility, on the order of 10 nm in persistence length, substantially influences the structure and thermodynamics of DNA–nanoparticle complex formation. Potential of mean force calculations quantify the thermodynamic preference for nanoparticle binding to more flexible DNA, with the free energy difference arising primarily from the sequence‐dependent elastic energy of DNA bending. We then turn to all‐atom simulations of DNA minicircles with approximately 90 base pairs. Sequence‐dependent coupling between DNA bending and its helical twist is identified for specific dinucleotide steps, and the internal dynamics of poloidal rotation and in‐plane circular vibration are characterized on time scales of tens and several nanoseconds, respectively. Finally, we present our recent investigations of mechanically interlocked DNA nanostructures: rotaxanes, in which a DNA minicircle is threaded onto a linear DNA axle, and catenanes, composed of two mutually interlocked DNA minicircles. The effects of torsional stress‐induced shape distortion on the structure and dynamics of these topologically constrained architectures are discussed. Together, these studies illustrate how the interplay of DNA sequence, flexibility, and topology governs the behavior of sharply bent DNA, providing molecular‐level insights for the design of DNA‐based nanoscale devices.