Molecular Dynamics Study of the Interaction of Carbon Nanotubes with Telomeric DNA Fragment Containing Noncanonical G-Quadruplex and i-Motif Forms

Tomasz Panczyk,Pawel Wolski,Patrycja Wojton

doi:10.3390/ijms21061925

Tomasz Panczyk, Pawel Wolski + Show 1 more

Open Access

https://doi.org/10.3390/ijms21061925

Copy DOI

Abstract

This work deals with molecular dynamics simulations of systems composed of telomeric dsDNA fragments, iG, and functionalized carbon nanotubes, fCNT. The iG contains 90 nucleotides in total and in its middle part the noncanonical i-motif and G-quadruplex are formed. Two chiralities of the fCNT were used, i.e., (10,0) and (20,0) and these nanotubes were either on-tip functionalized by guanine containing functional groups or left without functionalization. We proposed a dedicated computational procedure, based on the replica exchange concept, for finding a thermodynamically optimal conformation of iG and fCNT without destroying the very fragile noncanonical parts of the iG. We found that iG forms a V-shape spatial structure with the noncanonical fragments located at the edge and the remaining dsDNA strands forming the arms of V letter. The optimal configuration of iG in reference to fCNT strongly depends on the on-tip functionalization of the fCNT. The carbon nanotube without functionalization moves freely between the dsDNA arms, while the presence of guanine residues leads to immobilization of the fCNT and preferential location of the nanotube tip near the junction between the dsDNA duplex and i-motif and G-quadruplex. We also studied how the presence of fCNT affects the stability of the i-motif at the neutral pH when the cytosine pairs are nonprotonated. We concluded that carbon nanotubes do not improve the stability of the spatial structure of i-motif also when it is a part of a bigger structure like the iG. Such an effect was described in literature in reference to carboxylated nanotubes. Our current results suggest that the stabilization of i-motif is most probably related to easy formation of semiprotonated cytosine pairs at neutral pH due to interaction with carboxylated carbon nanotubes.

Highlights

The noncanonical DNA forms like i-motif [1,2,3], iM, or G-quadruplex, Gq [4,5,6], have attracted considerable attention mainly due to their switchable folding/unfolding property
The structures obtained from initial equilibration runs were subjected to additional treatment in order to find possibly most thermodynamically optimal configurations of fCNT and iG compounds
It is quite obvious that standard unbiased molecular dynamics runs lead to rather random configurations if the interactions within the system compounds are bigger than thermal energy

Summary

Introduction

The noncanonical DNA forms like i-motif [1,2,3], iM, or G-quadruplex, Gq [4,5,6], have attracted considerable attention mainly due to their switchable folding/unfolding property. It was reported that carboxylated single walled carbon nanotubes can selectively induce human telomeric iM formation [14]. That property was usually linked to the presence of G-quadruplexes in the telomeric region of DNA but not to the i-motif. It was observed that selective stabilization of iM by carboxylated CNT led to telomere uncapping and removal of telomere binding proteins which caused DNA damage response [15]. The biological role of i-motif is far less recognized than the role of G-quadruplex, which is known as telomerase inhibitor [5,6]. It was found that iM can exist in regulatory regions of genome in living cells at physiological conditions [17]

Objectives

Methods

Results

Conclusion