Effect of DNA Flexibility on Complex Formation of a Cationic Nanoparticle with Double-Stranded DNA

Abstract

We present extensive molecular dynamics simulations of a cationic nanoparticle and a double-stranded DNA molecule to discuss the effect of DNA flexibility on the complex formation of a cationic nanoparticle with double-stranded DNA. Martini coarse-grained models were employed to describe double-stranded DNA molecules with two different flexibilities and cationic nanoparticles with three different electric charges. As the electric charge of a cationic nanoparticle increases, the degree of DNA bending increases, eventually leading to the wrapping of DNA around the nanoparticle at high electric charges. However, a small increase in the persistence length of DNA by 10 nm requires a cationic nanoparticle with a markedly increased electric charge to bend and wrap DNA around. Thus, a more flexible DNA molecule bends and wraps around a cationic nanoparticle with an intermediate electric charge, whereas a less flexible DNA molecule binds to a nanoparticle with the same electric charge without notable bending. This work provides solid evidence that a small difference in DNA flexibility (as small as 10 nm in persistence length) has a substantial influence on the complex formation of DNA with proteins from a biological perspective and suggests that the variation of sequence-dependent DNA flexibility can be utilized in DNA nanotechnology as a new tool to manipulate the structure of DNA molecules mediated by nanoparticle binding.

Potential of Mean Force for DNA Wrapping Around a Cationic Nanoparticle

“…The soft elastic network model was used to maintain the base pairing of the DNA double helix by applying a harmonic force between the backbone beads and between a backbone bead and the first connected bead in each base. The overall particle types and parameters of DNA were presented in a paper by Marrink and co-workers , and in our recent paper . The parameters for a cationic NP are also presented in our recent paper .…”

“…The overall particle types and parameters of DNA were presented in a paper by Marrink and co-workers , and in our recent paper . The parameters for a cationic NP are also presented in our recent paper . The default Martini parameters and particle types were used for Na + and Cl – ions and Martini standard water and antifreeze particles .…”

“…Complex formations of a double-stranded DNA with associating molecules such as proteins, NPs, dendrimers, and polyamines have been investigated extensively using computer simulations with various models at different scales. ,,,,− MD simulations using all-atom models have provided detailed information on DNA binding with proteins and NPs. − However, all-atom MD simulations are too time-consuming and computationally demanding to investigate the dynamic process of DNA bending and wrapping around proteins and NPs, except for a few recent works. , Simple physics-based models of DNA and NPs have also been used to investigate DNA bending and wrapping around a cationic NP, where DNA is modeled as a semiflexible polymer chain and NP as a charged sphere. ,,,,− Due to the simplicity of the molecular description, simulations of long-time and large-scale processes concerning DNA wrapping have been enabled. In particular, by using a polymer chain model of DNA with flexibility variation, it was shown that a cationic NP wrapped around by DNA rolls along the DNA from less flexible to more flexible regions to reduce the elastic energy of DNA bending. , However, several critical assumptions were made regarding the molecular interactions of DNA and an NP.…”

“…Alternatively, CG models − of DNA and NPs can be used to investigate the complex formation, − where longer-time and larger-scale simulations are enabled compared with all-atom MD simulations. In these models, more detailed information on DNA–NP interactions is provided compared to simulations with simple physics-based models of DNA and NPs.…”

“…In these models, more detailed information on DNA–NP interactions is provided compared to simulations with simple physics-based models of DNA and NPs. Recently, using Martini CG models of a double-stranded DNA molecule and a cationic NP, the effect of DNA flexibility on the complex formation between the DNA and NP was investigated . The Martini CG model has DNA sequence specificity for flexibility variation, and molecular interactions are better described by explicitly including solvents and ions.…”