Entropic Penalties in Circular DNA Assembly

TL;DR

This paper introduces a new computational method to analyze the thermodynamic properties of circular DNA, revealing their intrinsic flexibility, multiple stable conformations, and the effects of sequence length on unwinding and bending stress.

Contribution

A novel path integral approach for real-space analysis of DNA circular molecules' thermodynamics and conformational flexibility.

Findings

Multiple stable conformations identified for short DNA sequences.

Shorter sequences exhibit higher bending stress and more pronounced unwinding.

Entropic effects of helix formation are quantitatively estimated.

Abstract

The thermodynamic properties of DNA circular molecules are investigated by a new path integral computational method which treats in the real space the fundamental forces stabilizing the molecule. The base pair and stacking contributions to the classical action are evaluated separately by simulating a broad ensemble of twisted conformations. We obtain, for two short sequences, a free energy landscape with multiple wells corresponding to the most convenient values of helical repeat. Our results point to a intrinsic flexibility of the circular structures in which the base pair fluctuations move the system from one well to the next thus causing the local unwinding of the helix. The latter is more pronounced in the shorter sequence whose cyclization causes a higher bending stress. The entropic reductions associated to the formation of the ordered helicoidal structure are estimated.