Subscribe to the gold package and get unlimited access to Shamra Academy
Register a new userFine-tuning the DNA conductance by intercalation of drug molecules
64
0
0.0
(
0
)
Ask ChatGPT about the research
No Arabic abstract
In this letter, we study the structure-transport property relationships of small ligand intercalated DNA molecules using a multiscale modelling approach where extensive ab-initio calculations are performed on numerous MD-simulated configurations of dsDNA and dsDNA intercalated with two different intercalators, ethidium and daunomycin. DNA conductance is found to increase by one order of magnitude upon drug intercalation due to the local unwinding of the DNA base pairs adjacent to the intercalated sites which leads to modifications of the density-of-states in the near-Fermi energy region of the ligand-DNA complex. Our study suggests that the intercalators can be used to enhance/tune the DNA conductance which opens new possibilities for their potential applications in nanoelectronics.
rate research
Read More
Most of the anticancer drugs bind to double-stranded DNA (dsDNA) by intercalative-binding mode. Although experimental studies have become available recently, a molecular-level understanding of the interactions between the drug and dsDNA that lead to the stability of the intercalated drug is lacking. Of particular interest are the modifications of the mechanical properties of dsDNA observed in experiments. The latter could affect many biological functions, such as DNA transcription and replication. Here we probe, via all-atom molecular dynamics (MD) simulations, change in the mechanical properties of intercalated drug-DNA complexes for two intercalators, daunomycin and ethidium. We find that, upon drug intercalation, stretch modulus of DNA increases significantly, whereas its persistence length and bending modulus decrease. Steered MD simulations reveal that it requires higher forces to stretch the intercalated dsDNA complexes than the normal dsDNA. Adopting various pulling protocols to study force-induced DNA melting, we find that the dissociation of dsDNA becomes difficult in the presence of intercalators. The results obtained here provide a plausible mechanism of function of the anticancer drugs, i.e., via altering the mechanical properties of DNA. We also discuss long-time consequences of using these drugs, which require further in vivo investigations.
The dispersion interaction between a pair of parallel DNA double-helix structures is investigated by means of the van der Waals density functional (vdW-DF) method. Each double-helix structure consists of an infinite repetition of one B-DNA coil with 10 base pairs. This parameter-free density functional theory (DFT) study illustrates the initial step in a proposed vdW-DF computational strategy for large biomolecular problems. The strategy is to first perform a survey of interaction geometries, based on the evaluation of the van der Waals (vdW) attraction, and then limit the evaluation of the remaining DFT parts (specifically the expensive study of the kinetic-energy repulsion) to the thus identified interesting geometries. Possibilities for accelerating this second step is detailed in a separate study. For the B-DNA dimer, the variation in van der Waals attraction is explored at relatively short distances (although beyond the region of density overlap) for a 360 degrees rotation. This study highlights the role of the structural motifs, like the grooves, in enhancing or reducing the vdW interaction strength. We find that to a first approximation, it is possible to compare the DNA double strand at large wall-to-wall separations to the cylindrical shape of a carbon nanotube (which is almost isotropic under rotation). We compare our first-principles results with the atom-based dispersive interaction predicted by DFT-D2 [J. Comp. Chem. 27, 1787 (2006)] and find agreement in the asymptotic region. However, we also find that the differences in the enhancement that occur at shorter distances reveal characteristic features that result from the fact that the vdW-DF method is an electron-based (as opposed to atom-based) description.
The effective force between two parallel DNA molecules is calculated as a function of their mutual separation for different valencies of counter- and salt ions and different salt concentrations. Computer simulations of the primitive model are used and the shape of the DNA molecules is accurately modelled using different geometrical shapes. We find that multivalent ions induce a significant attraction between the DNA molecules whose strength can be tuned by the averaged valency of the ions. The physical origin of the attraction is traced back either to electrostatics or to entropic contributions. For multivalent counter- and monovalent salt ions, we find a salt-induced stabilization effect: the force is first attractive but gets repulsive for increasing salt concentration. Furthermore, we show that the multivalent-ion-induced attraction does not necessarily correlate with DNA overcharging.
During the last decade coarse-grained nucleotide models have emerged that allow us to DNA and RNA on unprecedented time and length scales. Among them is oxDNA, a coarse-grained, sequence-specific model that captures the hybridisation transition of DNA and many structural properties of single- and double-stranded DNA. oxDNA was previously only available as standalone software, but has now been implemented into the popular LAMMPS molecular dynamics code. This article describes the new implementation and analyses its parallel performance. Practical applications are presented that focus on single-stranded DNA, an area of research which has been so far under-investigated. The LAMMPS implementation of oxDNA lowers the entry barrier for using the oxDNA model significantly, facilitates future code development and interfacing with existing LAMMPS functionality as well as other coarse-grained and atomistic DNA models.
We report a theoretical study of DNA flexibility and quantitatively predict the ring closure probability as a function of DNA contour length. Recent experimental studies show that the flexibility of short DNA fragments (as compared to the persistence length of DNA l_P~150 base pairs) cannot be described by the traditional worm-like chain (WLC) model, e.g., the observed ring closure probability is much higher than predicted. To explain these observations, DNA flexibility is investigated with explicit considerations of a new length scale l_D~10 base pairs, over which DNA local bend angles are correlated. In this correlated worm-like chain (C-WLC) model, a finite length correction term is analytically derived and the persistence length is found to be contour length dependent. While our model reduces to the traditional worm-like chain model when treating long DNA at length scales much larger than l_P, it predicts that DNA becomes much more flexible at shorter sizes, which helps explain recent cyclization measurements of short DNA fragments around 100 base pairs.
Log in to be able to interact and post comments
comments
Fetching comments
Sign in to be able to follow your search criteria
