Data-Driven Approaches to Predict Dendrimer Cytotoxicity.

Dendrimers are employed as functional elements in contrast agents and are proposed as nontoxic vehicles for drug delivery. Toxicity is a property that is to be evaluated for this novel class of bionanomaterials for in vivo applications. The current research is hampered due to the lack of structured data sets for toxicity studies for dendrimers. In this work, we have built a data set by curating literature for toxicity data and augmented it with structural and physicochemical features. We present a comprehensive, feature-rich database of dendrimer toxicity measured across various cell lines for prediction, design, and optimization studies. We have also explored novel computational approaches for predicting dendrimer cytotoxicity. We demonstrate superior outcomes for toxicity prediction using essential regression in the space of small data sets.

Dynamics of terminal fraying-peeling and hydrogen bonds dictates the sequential vs. cooperative melting pathways of nanoscale DNA and PNA triplexes.

Peptide nucleic acids (PNAs) are charge-neutral synthetic DNA/RNA analogues. In many aspects of biology and biotechnology, the details of DNA and PNA melting reaction coordinates are crucial, and their associative/dissociative details remain inadequately understood. In the current study, we have attempted to gain insights into comparative melting pathways and binding affinity of iso-sequences of an 18-mer PNA-DNA-PNA triplex and the analogous DNA-DNA-DNA triplex, and DNA-DNA and PNA-DNA duplexes. It is intriguing that while the DNA-DNA-DNA triplex melts in two sequential steps, the PNA-DNA-PNA triplex melts in a single step and the mechanistic aspects for this difference are still not clear. We report an all-atom molecular dynamics simulation of both complexes in the temperature range of 300 to 500 K with 20 K intervals. Based on the trajectory analysis, we provide evidence that the association and dissociation are dictated by the differences in fraying-peeling effects from either terminus to the center in a zipper pattern among the PNA-DNA-PNA triplex and DNA-DNA-DNA triplexes. These are shown to be governed by the different characteristics of H-bonding, RMSD, and Free Energy Landscape (FEL) as analyzed by PCA, leading to the DNA-DNA-DNA triplex exhibiting sequential melting, while the PNA-DNA-PNA triplex shows cooperative melting of the whole fragment in a single-step. The PNA-DNA-PNA triplex base pairs are thermodynamically more stable than the DNA-DNA-DNA triplex, with the binding affinity of PNA-TFO to the PNA : DNA duplex being higher than that of DNA-TFO to the DNA : DNA duplex. The investigation of the association/dissociation of PNA-TFO to the PNA-DNA duplex has relevance and importance in the emerging effective applications of oligonucleotide therapy.

Stability of the chiral crystal phase and breakdown of the cholesteric phase in mixtures of active-passive chiral rods.

In this study, we aim to explore the effect of chirality on the phase behavior of active helical particles driven by two-temperature scalar activity. We first calculate the equation of state of soft helical particles of various intrinsic chiralities using molecular dynamics (MD) simulation. In equilibrium, the emergence of various liquid crystal (LC) phases such as nematic (N), cholesteric , smectic (Sm) and crystal (K) crucially depends on the presence of walls that induce planar alignment. Next, we introduce activity through the two-temperature model: keep increasing the temperature of half of the helical particles (labeled as 'hot' particles) while maintaining the temperature of the other half at a lower value (labeled as 'cold' particles). Starting from a homogeneous isotropic (I) phase, we find the emergence of 2-TIPS: two temperature-induced phase separations between the hot and cold particles. We also observe that the cold particles undergo an ordering transition to various LC phases even in the absence of a wall. This observation reveals that the hot-cold interface in the active system plays the role of a wall in the equilibrium system by inducing an alignment direction for the cold particles. However, in the case of a cholesteric phase, we observe that activity destabilizes the phase by inducing smectic ordering in the cold zone while an isotropic structure in the hot zone. The smectic ordering in the cold zone eventually transforms to a chiral crystal phase with high enough activity.

Molecular dynamics simulations show how antibodies may rescue HIV-1 mutants incapable of infecting host cells.

High mutation and replication rates of HIV-1 result in the continuous generation of variants, allowing it to adapt to changing host environments. Mutations often have deleterious effects, but variants carrying them are rapidly purged. Surprisingly, a particular variant incapable of entering host cells was found to be rescued by host antibodies targeting HIV-1. Understanding the molecular mechanism of this rescue is important to develop and improve antibody-based therapies. To unravel the underlying mechanisms, we performed fully atomistic molecular dynamics simulations of the HIV-1 gp41 trimer responsible for viral entry into host cells, its entry-deficient variant, and its complex with the rescuing antibody. We find that the Q563R mutation, which the entry-deficient variant carries, prevents the native conformation of the gp41 6-helix bundle required for entry and stabilizes an alternative conformation instead. This is the consequence of substantial changes in the secondary structure and interactions between the domains of gp41. Binding of the antibody F240 to gp41 reverses these changes and re-establishes the native conformation, resulting in rescue. To test the generality of this mechanism, we performed simulations with the entry-deficient L565A variant and antibody 3D6. We find that 3D6 binding was able to reverse structural and interaction changes introduced by the mutation and restore the native gp41 conformation. Viral variants may not only escape antibodies but be aided by them in their survival, potentially compromising antibody-based therapies, including vaccination and passive immunization. Our simulation framework could serve as a tool to assess the likelihood of such resistance against specific antibodies.Communicated by Ramaswamy H. SarmaCommunicated by Ramaswamy H. Sarma.

DNA groove preference shift upon phosphorylation of a protamine-like cationic peptide.

Protamines, arginine-rich DNA-binding proteins, are responsible for chromatin compaction in sperm cells, but their DNA groove preference, major or minor, is not clearly identified. We herein study the DNA groove preference of a short protamine-like cationic peptide before and after phosphorylation, using all-atom molecular dynamics and umbrella sampling simulations. According to various thermodynamic and structural analyses, a peptide in its non-phosphorylated native state prefers the minor groove over the major groove, but phosphorylation of the peptide bound to the minor groove not only reduces its binding affinity but also brings a serious deformation of the minor groove, eliminating the minor-groove preference. As protamines are heavily phosphorylated before binding to DNA, we expect that the structurally disordered phosphorylated protamines would prefer major grooves to enter into DNA during spermatogenesis.

Trajectory-Extending Kinetic Monte Carlo Simulations to Evaluate Pure and Gas Mixture Diffusivities through a Dense Polymeric Membrane.

With renewed interest in CO2 separations, carbon molecular sieving (CMS) membrane performance evaluation requires diffusion coefficients as inputs to have a reliable estimate of the permeability. An optimal material is desired to have both high selectivity and permeability. Gases diffusing through dense CMS and polymeric membranes experience extended subdiffusive regimes, which hinders reliable extraction of diffusion coefficients from mean squared displacement data. We improve the sampling of the diffusive landscape by implementing the trajectory-extending kinetic Monte Carlo (TEKMC) technique to efficiently extend molecular dynamics (MD) trajectories from ns to µs time scales. The obtained self-diffusion coefficient of pure CO2 in CMS membranes derived from a 6FDA/BPDA-DAM precursor polymer melt is found to linearly increase from 0.8-1.3 × 10-6 cm2 s-1 in the pressure range of 1-20 bar, which supports previous experimental findings. We also extended the TEKMC algorithm to evaluate the mixture diffusivities in binary mixtures to determine the permselectivity of CO2 in CH4 and N2 mixtures. The mixture diffusion coefficient of CO2 ranges from 1.3-7 × 10-6 cm2 s-1 in the binary mixture CO2/CH4, which is significantly higher than the pure gas diffusion coefficient. Robeson plot comparisons show that the permselectivity obtained from pure gas diffusion data is significantly lower than that predicted using mixture diffusivity data. Specifically, in the case of the CO2/N2 mixture, we find that using mixture diffusivities led to permselectivities lying above the Robeson limit highlighting the importance of using mixture diffusivity data for an accurate evaluation of the membrane performance. Combined with gas solubilities obtained from grand canonical Monte Carlo (GCMC) simulations, our work shows that simulations with the TEKMC method can be used to reliably evaluate the performance of materials for gas separations.

Gold nanoparticles aggregation on graphene using Reactive force field: A molecular dynamic study.

We examine the aggregation behavior of AuNPs of different sizes on graphene as function of temperature using molecular dynamic simulations with Reax Force Field. In addition, the consequences of such aggregation on the morphology of AuNPs and the charge transfer behavior of AuNP-Graphene hybrid structure are analyzed. The aggregation of AuNPs on graphene is confirmed from the center of mass distance calculation. The simulation results indicate that the size of AuNPs and temperature significantly affect the aggregation behavior of AuNPs on graphene. The strain calculation showed that shape of AuNPs changes due to the aggregation and the smaller size AuNPs on graphene exhibit more shape changes than larger AuNPs at all the temperatures studies in this work. The charge transfer calculation reveals that, the magnitude of charge transfer is higher for larger AuNPs-graphene composite when compared with smaller AuNPs-graphene composite. The charge transfer trend and the trends seen in the number of Au atoms directly in touch with graphene are identical. Hence, our results conclude that, quantity of Au atoms directly in contact with graphene during aggregation is primarily facilitates charge transfer between AuNPs and graphene. Our results on the size dependent strain and charge transfer characteristics of AuNPs will aid in the development of AuNPs-graphene composites for sensor applications.

Effect of confinement and topology: 2-TIPS vs. MIPS.

2-TIPS (two temperature induced phase separation) refers to the phase separation phenomenon observed in mixtures of active and passive particles which are modelled using scalar activity. The active particles are connected to a thermostat at high temperature while the passive particles are connected to the thermostat at low temperature and the relative temperature difference between "hot" and "cold" particles is taken as the measure of the activity χ of the non-equilibrium system. The study of such binary mixtures of hot and cold particles under various kinds of confinement is an important problem in many physical and biological processes. The nature and extent of phase separation are heavily influenced by the geometry of confinement, activity, and density of the non-equilibrium binary mixture. Investigating such 3D binary mixtures confined by parallel walls, we observe that the active and passive particles phase separate, but the extent of phase separation is reduced compared to bulk phase separation at high densities and enhanced at low densities. However, when the binary mixture of active and passive particles is confined inside a spherical cavity, the phase separation is radial for small radii of the confining sphere and the extent of phase separation is higher compared to their bulk counterparts. Confinement leads to interesting properties in the passive (cold) region like enhanced layering and high compression in the direction parallel to the confining wall. In 2D, both the bulk and confined systems of the binary mixture show a significant decrement in the extent of phase separation at higher densities. This observation is attributed to the trapping of active particles inside the passive cluster, which increases with density. Thus the 2D systems show structures more akin to dense-dilute phase co-existence, which is observed in motility induced phase separation in 2D active systems. The binary mixture constrained on the spherical surface also shows similar phase co-existence. Our analyses reveal that the coexistent densities observed in 2-TIPS on the spherical surface agree with the findings of previous studies on MIPS in active systems on a sphere.

Entropy of different phases formed by soft rods.

The computation of entropy in liquids and liquid crystal (LC) phases is a big challenge in statistical physics. In this work, we extend the two-phase thermodynamic model (2PT) to shape anisotropic soft repulsive spherocylinders (SRSs) and report the absolute values of entropy for different LC phases for a range of aspect ratios L/D = 2 - 5. We calculate the density of states for different LC phases and decompose it into contributions arising from translational and rotational degrees of freedom. The translational and rotational modes are further partitioned into diffusive, gas-like, and non-diffusive, solid-like components using a fluidicity factor. In the dilute limit, the entropy values obtained from the 2PT method match exactly those of an ideal rigid rotor. We find that, for a given packing fraction, the magnitude of the total entropy is roughly equal regardless of the different LC phases associated with different aspect ratios. We also compute the excess entropy (for L/D = 5) and compare those with the values obtained using the standard integration approach of MD or Monte Carlo equation of state of SRS. The values obtained using both approaches match very well. The rotational and translational fluidicity factors are further used to determine the phase boundaries of different LC phases.

Utilization of DNA and 2D metal oxide interaction for an optical biosensor.

The efficient monitoring and early detection of viruses may provide essential information about diseases. In this work, we have highlighted the interaction between DNA and a two-dimensional (2D) metal oxide for developing biosensors for further detection of viral infections. Spectroscopic measurements have been used to probe the efficient interactions between single-stranded DNA (ssDNA) and the 2D metal oxide and make them ideal candidates for detecting viral infections. We have also used fully atomistic molecular dynamics (MD) simulation to give a microscopic understanding of the experimentally observed ssDNA-metal oxide interaction. The adsorption of ssDNA on the inorganic surface was found to be driven by favourable enthalpy change, and 5'-guanine was identified as the interacting nucleotide base. Additionally, the in silico assessment of the conformational changes of the ssDNA chain during the adsorption process was also performed in a quantitative manner. Finally, we comment on the practical implications of these developments for sensing that could help design advanced systems for preventing virus-related pandemics.

Efficient Removal of Uranyl Ions Using PAMAM Dendrimer: Simulation and Experiment.

In this work, using atomistic molecular dynamics (MD) simulations and polymer-assisted ultrafiltration experiments, we explore the adsorption and removal of uranyl ions from aqueous solutions using poly(amidoamine) (PAMAM) dendrimers. The effects of uranyl ion concentration and the pH of the solution were examined for PAMAM dendrimers of generations 3, 4, and 5. Our simulation results show that PAMAM has a high adsorption capacity for the uranyl ions. The adsorption capacity increases with increasing concentration of uranyl ions for all 3 generations of PAMAM in agreement with experimental findings. We find that the number of uranyl ions bound to PAMAM is significantly higher in acidic solutions (pH < 3) as compared to neutral solutions (pH ∼ 7) for all uranyl ion concentrations. Additionally, we find an increase in the number of adsorbed uranyl ions to PAMAM with the increase in the dendrimer generation. This increase is due to the greater number of binding sites present for higher-generation PAMAM dendrimers. Our simulation study shows that nitrate ions form a solvation shell around uranyl ions, which allows them to bind to PAMAM binding sites, including the amide, amine, and carbonyl groups. In polymer-assisted ultrafiltration (PAUF) experiments, the removal percentage of uranyl ions by G3 PAMAM dendrimer increased from 36.3% to 42.6% as the metal ion concentration increased from 2.1 × 10-5 M to 10.5 × 10-5 M at a pH of 2. Our combined experiment and simulation study suggests that PAMAM is an effective adsorbent for removing uranyl ions from aqueous solutions.

Phase behavior of active and passive dumbbells.

We report phase separation in a mixture of "hot" and "cold" three-dimensional dumbbells which interact by Lennard-Jones potential. We also have studied the effect of asymmetry of dumbbells and the variation of ratio of "hot" and "cold" dumbbells on their phase separation. The ratio of the temperature difference between hot and cold dumbbells to the temperature of cold dumbbells is a measure of the activity χ of the system. From constant density simulations of symmetric dumbbells, we observe that the "hot" and "cold" dumbbells phase separate at higher activity ratio (χ>5.80) compared to that of a mixture of hot and cold Lennard-Jones monomers (χ>3.44). We find that, in the phase-separated system, the hot dumbbells have high effective volume and hence high entropy which is calculated by two-phase thermodynamic method. The high kinetic pressure of hot dumbbells forces the cold dumbbells to form dense clusters such that at the interface the high kinetic pressure of hot dumbbells is balanced by the virial pressure of cold dumbbells. We find that phase separation pushes the cluster of cold dumbbells to have solidlike ordering. Bond orientation order parameters reveal that the cold dumbbells form solidlike ordering consisting of predominantly face-centered cubic and hexagonal-close packing packing, but the individual dumbbells have random orientations. The simulation of the nonequilibrium system of symmetric dumbbells at different ratios of number of hot dumbbells to cold dumbbells reveals that the critical activity of phase separation decreases with increase in fraction of hot dumbbells. The simulation of equal mixture of hot and cold asymmetric dumbbells revealed that the critical activity of phase separation was independent of the asymmetry of dumbbells. We also observed that the clusters of cold asymmetric dumbbells showed both crystalline and noncrystalline order depending on the asymmetry of dumbbells.

Two-temperature activity induces liquid-crystal phases inaccessible in equilibrium.

In equilibrium hard-rod fluids, and in effective hard-rod descriptions of anisotropic soft-particle systems, the transition from the isotropic (I) phase to the nematic phase (N) is observed above the rod aspect ratio L/D=3.70 as predicted by Onsager. We examine the fate of this criterion in a molecular dynamics study of a system of soft repulsive spherocylinders rendered active by coupling half the particles to a heat bath at a higher temperature than that imposed on the other half. We show that the system phase-separates and self-organizes into various liquid-crystalline phases that are not observed in equilibrium for the respective aspect ratios. In particular, we find a nematic phase for L/D=3 and a smectic phase for L/D=2 above a critical activity.

Mechanistic insight into the structure, thermodynamics and dynamics of equilibrium gels of multi-armed DNA nanostars.

The unique sequence specificity rule of DNA makes it an ideal molecular building block for constructing periodic arrays and devices with nanoscale accuracy and precision. Here, we present the self-assembly of DNA nanostars having three, four and five arms into a gel phase using a simplistic coarse-grained bead-spring model developed by Z. Xing, C. Ness, D. Frenkel and E. Eiser (Macromolecules, 2019, 52, 504-512). Our simulations show that the DNA nanostars form a thermodynamically stable fully bonded gel phase from an unstructured liquid phase with the lowering of temperature. We characterize the phase transition by calculating several structural features such as the radial distribution function and structure factor. The thermodynamics of gelation is quantified by the potential energy and translational pair-entropy of the system. The phase transition from an arrested gel phase to an unstructured liquid phase has been modelled using a two-state theoretical model. We find that this transition is enthalpy driven, and loss of configuration and translational entropy is counterpoised by enthalpic interaction of the DNA sticky-ends, which gives rise to a gel phase at low temperature. The absolute rotational and translational entropy of the systems, measured using a two-phase thermodynamic model, also substantiates the gel transition. The slowing down of the dynamics upon approaching the transition temperature from a high temperature demonstrates the phase transition to a gel phase. A detailed numerical simulation study of the morphology, dynamics and thermodynamics of DNA gelation can provide guidance for future experiments, is easily extensible to other polymeric systems, and is expected to help in understanding the physics of self-assembly.

Does twist angle affect the properties of water confined inside twisted bilayer graphene?

Graphene nanoslit pores are used for nanofluidic devices, such as, in water desalination, ion-selective channels, ionic transistors, sensing, molecular sieving, blue energy harvesting, and protein sequencing. It is a strenuous task to prepare nanofluidic devices, because a small misalignment leads to a significant alteration in various properties of the devices. Here, we focus on the rotational misalignment between two parallel graphene sheets. Using molecular dynamics simulation, we probe the structure and dynamics of monolayer water confined inside graphene nanochannels for a range of commensurate twist angles. With SPC/E and TIP4P/2005 water models, our simulations reveal the independence of the equilibrium number density- n ∼ 13 nm-2 for SPC/E and n ∼ 11.5 nm-2 for TIP4P/2005- across twists. Based on the respective densities of the water models, the structure and dielectric constant are invariant of twist angles. The confined water structure at this density shows square ice ordering for SPC/E water only. TIP4P/2005 shows ordering at the vicinity of a critical density (n ∼ 12.5 nm-2). The average perpendicular dielectric constant of the confined water remains anomalously low (∼2 for SPC/E and ∼6 for TIP4P/2005) for the studied twist angles. We find that the friction coefficient of confined water molecules varies for small twist angles, while becoming independent for twists greater than 5.1°. Our results indicate that a small, angular misalignment will not impair the dielectric properties of monolayer water within a graphene slit-pore, but can significantly influence its dynamics.

Packing and emergence of the ordering of rods in a spherical monolayer.

Spatially ordered systems confined to surfaces such as spheres exhibit interesting topological structures because of curvature induced frustration in orientational and translational order. The study of these structures is important for investigating the interplay between the geometry, topology, and elasticity, and for their potential applications in materials science, such as engineering directionally binding particles. In this work, we numerically simulate a spherical monolayer of soft repulsive spherocylinders (SRSs) and study the packing of rods and their ordering transition as a function of the packing fraction. In the model that we study, the centers of mass of the spherocylinders (situated at their geometric centers) are constrained to move on a spherical surface. The spherocylinders are free to rotate about any axis that passes through their respective centers of mass. We show that, up to moderate packing fractions, a two dimensional liquid crystalline phase is formed whose orientational ordering increases continuously with increasing density. This monolayer of orientationally ordered SRS particles at medium densities resembles a hedgehog-long axes of the SRS particles are aligned along the local normal to the sphere. At higher packing fractions, the system undergoes a transition to the solid phase, which is riddled with topological point defects (disclinations) and grain boundaries that divide the whole surface into several domains.

A computational study on strontium ion modified hydroxyapatite-fibronectin interactions.

Protein adsorption is the first key step in cell-material interactions. The initial phase of such an adsorption process can only be probed using modelling approaches like molecular dynamics (MD) simulations. Despite a large number of studies on the adsorption behaviour of proteins on different biomaterials including calcium phosphates (CaP), little attention has been paid towards the quantitative assessment of the effects of various physicochemical influencers like surface modification, pH, and ionic strength. In the case of doped CaPs, surface modification through isomorphic substitution of foreign ions inside the apatite structure is of particular interest in the context of protein-HA interactions, as it is widely used to tailor the biological response of HA. Given this background, we present here the molecular-level understanding of the fibronectin (FN) adsorption mechanism and kinetics on a Sr2+-doped hydroxyapatite, HA, (001) surface at 300 K by means of all-atom molecular dynamics simulations. Electrostatic interactions involved in the adsorption of FN on HA were found to be significantly modified due to Sr2+ doping into the apatite lattice. In harmony with the published experimental observations, the Sr-doped surfaces were found to better support FN adhesion compared to pure HA, with 10 mol% Sr-doped HA exhibiting the best FN adsorption. The observed altered adsorption behaviour of FN on Sr-doped HA was correlated with the Hofmeister effect. Moreover, the non-monotonous trend of the FN-material interaction energy can be attributed to the spatial rearrangement of the functional groups (PO43-, OH-) in the apatite crystal. Sr2+ ions also influence the stability of the secondary structure of FN, as observed from the root mean square deviation (RMSD) and root mean square fluctuation (RMSF) analysis. The presence of Sr2+ enhances the flexibility of specific residues (residue nos. 20-44, 74-88) of the FN module. Rupture forces to disentangle FN from the biomaterial surface, obtained from steered molecular dynamics (SMD) simulations, were found to corroborate well with the results of equilibrium MD simulations. One particular observation is that the availability of an RGD motif (Arginine-Glycine-aspartate sequence, which interacts with cell surface receptor integrin to form a focal adhesion complex) for the interaction with cell surface receptor integrin is not significantly influenced by Sr2+ substitution.

Effect of phosphorylation of protamine-like cationic peptide on the binding affinity to DNA.

Protamines are more arginine-rich and more basic than histones and are responsible for providing a highly compacted shape to the sperm heads in the testis. Phosphorylation and dephosphorylation are two events that occur in the late phase of spermatogenesis before the maturation of sperms. In this work, we have studied the effect of phosphorylation of protamine-like cationic peptides using all-atom molecular dynamics simulations. Through thermodynamic analyses, we found that phosphorylation reduces the binding efficiency of such cationic peptides on DNA duplexes. Peptide phosphorylation leads to a less efficient DNA condensation, due to a competition between DNA-peptide and peptide-peptide interactions. We hypothesize that the decrease of peptide bonds between DNA together with peptide self-assembly might allow an optimal re-organization of chromatin and an efficient condensation through subsequent peptide dephosphorylation. Based on the globular and compact conformations of phosphorylated peptides mediated by arginine-phosphoserine H-bonding, we furthermore postulate that phosphorylated protamines could more easily intrude into chromatin and participate to histone release through disruption of histone-histone and histone-DNA binding during spermatogenesis.

Selection of start codon during mRNA scanning in eukaryotic translation initiation.

Accurate and high-speed scanning and subsequent selection of the correct start codon are important events in protein synthesis. Eukaryotic mRNAs have long 5' UTRs that are inspected for the presence of a start codon by the ribosomal 48S pre-initiation complex (PIC). However, the conformational state of the 48S PIC required for inspecting every codon is not clearly understood. Here, atomistic molecular dynamics (MD) simulations and energy calculations suggest that the scanning conformation of 48S PIC may reject all but 4 (GUG, CUG, UUG and ACG) of the 63 non-AUG codons, and initiation factor eIF1 is crucial for this discrimination. We provide insights into the possible role of initiation factors eIF1, eIF1A, eIF2α and eIF2ß in scanning. Overall, the study highlights how the scanning conformation of ribosomal 48S PIC acts as a coarse selectivity checkpoint for start codon selection and scans long 5' UTRs in eukaryotic mRNAs with accuracy and high speed.

Molecular Rectifiers with a Very High Rectification Ratio Enabled by Oxidative Damage in Double-Stranded DNA.

In this work, we report a novel strategy to construct highly efficient molecular diodes using oxidatively damaged DNA molecules. Being exposed to several endogenous and exogenous events, DNA suffers from constant oxidative damage, leading to the oxidation of guanine to 8-oxoguanine (8oxoG). Here, we study the charge migration properties of native and oxidatively damaged DNA using a multiscale multiconfigurational methodology comprising molecular dynamics, density functional theory, and kinetic Monte Carlo simulations. We perform a comprehensive study to understand the effect of different concentrations and locations of 8oxoG in a dsDNA sequence on its charge-transport properties and find tunable rectifier properties having potential applications in molecular electronics such as molecular switches and molecular rectifiers. We also discover the negative differential resistance properties of the fully oxidized Drew-Dickerson sequence. The presence of 8oxoG guanine leads to the trapping of charge, thus operating as a charge sink, which reveals how oxidized guanine saves the rest of the genome from further oxidative damage.