The Effects of Flexibility on dsDNA–dsDNA Interactions

Abstract

A detailed understanding of the physical mechanism of ion-mediated dsDNA interactions is important in biological functions such as DNA packaging and homologous pairing. We report the potential of mean force (PMF) or the effective solvent mediated interactions between two parallel identical dsDNAs as a function of interhelical separation in 0.15 M NaCl solution. Here, we study the influence of flexibility of dsDNAs on the effective interactions by comparing PMFs between rigid models and flexible ones. The role of flexibility of dsDNA pairs in their association is elucidated by studying the energetic properties of Na+ ions as well as the fluctuations of ions around dsDNAs. The introduction of flexibility of dsDNAs softens the vdW contact wall and induces more counterion fluctuations around dsDNAs. In addition, flexibility facilitates the Na+ ions dynamics affecting their distribution. The results quantify the extent of attraction influenced by dsDNA flexibility and further emphasize the importance of non-continuum solvation approaches.

Computational Modeling of DNA 3D Structures: From Dynamics and Mechanics to Folding

“…However, since deep learning models require large datasets for training, the limited number of known DNA structures challenges the application of these methods in DNA modeling. With the development of advanced hardware, highly accurate force fields, large amounts of experimental data, and refined computer modeling techniques, DNA modeling has the potential to not only explain a large number of experimental results [ 69 , 86 , 87 ], but also to serve as a guiding tool for new and exciting discoveries [ 159 , 160 ].…”

“…In recent years, MD simulations have been widely used to study the flexibility of DNAs, as DNA structural flexibility is closely associated with many biological processes involving the storage or encoding of genetic information [ 65 , 66 ]. Although many results from single-molecule experiments can be well-described by the commonly accepted WLC models [ 27 , 28 , 29 ], atomistic MD simulations are extensively used to obtain microscopic descriptions of DNA flexibility, such as the width and depth of the major/minor grooves and the distances/twist angles between neighbor base pairs [ 67 , 68 , 69 ]. For example, to explain the experimental results that short DNAs consisting of tens of base pairs (bps) may have seemingly higher flexibility than those of kilobase pairs, Wu et al performed MD simulations for short dsDNAs with a finite-length of 5–50 bps using the Amber parmbsc0 force field.…”