Quantifying the impact of simple DNA parameters on the cyclization J-factor for single-basepair-addition families

Yunjin Tong,Robert S Manning

doi:10.1038/s41598-018-22502-7

Abstract

We use Monte Carlo simulation to quantify the change in cyclization J-factor within a dramatically simplified model of DNA that involves parameters for uniform stiffnesses, intrinsic twist, and intrinsic bending (including nonplanar bending). Plots of J versus DNA length over multiple periods of helical repeat are fit to a simple functional form in order to project the behavior of J over a broad range of these model parameters. In some instances, this process allows us to find families of DNA molecules (within our model) with quite different material properties, but very similar plots of J versus length, so similar as to likely to be indistinguishable by experiments. This effect is seen both for the parameter-pair of bend angle and stiffness scaling, as well as for the parameter-trio of helical repeat, bend angle, and bend non-planarity.

Highlights

In this article, we perform Monte Carlo computations that correspond to this style of experiment, computing what we will call the cyclization profile of a DNA sequence: the plot of J versus DNA length when adding single basepairs to the sequence under study
In addition to the works cited above, many of which paired experimental results with computational studies akin to our approach, there is the early work of Shimada and Yamakawa8, who studied the dependence of J over a long range of lengths for uniform unbent DNA, and Levene and Crothers9, who translated the statistical-mechanical theory of J-factors from Jacobson, Stockmayer, and Flory et al.10,11 into a Monte Carlo computation that is related to our approach
There was the study by Zhang and Crothers12, which included results relating J to curvature and helical repeat, with J computed via a new harmonic approximation, the work by Towles et al.13, which used Monte Carlo computations to study J as a function of length for looping in the presence of

Summary

Introduction

We perform Monte Carlo computations that correspond to this style of experiment, computing what we will call the cyclization profile of a DNA sequence: the plot of J versus DNA length when adding single basepairs to the sequence under study. In terms of the dependencies of the J-factor on each parameter studied, many of the effects are intuitive, but still its quantification allows a useful “calibration”, e.g., one can take J-factor computations coming from recent models with hundreds or thousands of parameters and align them with a simple model with just a few, more intuitive, parameters. Our study is connected to Czapla, Swigon and Olson, both in methodology (as we use an adaptation of their version of the Alexandrowicz half-molecule trick to develop high-accuracy computations) and in a focus on the dependence of the cyclization profile on a few relatively simple parameters ( our parameters of study differ)

Objectives

Methods

Results

Conclusion