Free energy landscape and characteristic forces for the initiation of DNA unzipping

TL;DR

This study combines simulations and models to analyze the initial forces and free energy landscape involved in DNA unzipping, revealing high force requirements and microscopic details of the first base pair separation.

Contribution

It provides detailed atomistic and coarse-grained insights into the force and free energy barriers of the initial DNA unzipping step, which were previously unclear.

Findings

Initial unzipping requires forces of 130-230 pN.

A force echo of ~50 pN occurs at the second base pair.

High force peaks are due to entropic effects in free energy basins.

Abstract

DNA unzipping, the separation of its double helix into single strands, is crucial in modulating a host of genetic processes. Although the large-scale separation of double-stranded DNA has been studied with a variety of theoretical and experimental techniques, the minute details of the very first steps of unzipping are still unclear. Here, we use atomistic molecular dynamics (MD) simulations, coarse-grained simulations and a statistical-mechanical model to study the initiation of DNA unzipping by an external force. The calculation of the potential of mean force profiles for the initial separation of the first few terminal base pairs in a DNA oligomer reveal that forces ranging between 130 and 230 pN are needed to disrupt the first base pair, values of an order of magnitude larger than those needed to disrupt base pairs in partially unzipped DNA. The force peak has an "echo," of approximately 50 pN, at the distance that unzips the second base pair. We show that the high peak needed to initiate unzipping derives from a free energy basin that is distinct from the basins of subsequent base pairs because of entropic contributions and we highlight the microscopic origin of the peak. Our results suggest a new window of exploration for single molecule experiments.