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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Role of entropy in determining the phase behavior of protein solutions induced by multivalent ions.

Recent experiments have reported lower critical solution temperature (LCST) phase behavior of aqueous solutions of proteins induced by multivalent ions, where the solution phase separates upon heating. This phenomenon is linked to complex hydration effects that result in a net entropy gain upon phase separation. To decipher the underlying molecular mechanism, we use all-atom molecular dynamics simulations along with the two-phase thermodynamic method for entropy calculation. Based on simulations of a single BSA protein in various salt solutions (NaCl, CaCl2, MgCl2, and YCl3) at temperatures (T) ranging 283-323 K, we find that the cation-protein binding affinity increases with T, reflecting its thermodynamic driving force to be entropic in origin. We show that in the cation binding process, many tightly bound water molecules from the solvation shells of a cation and the protein are released to the bulk, resulting in entropy gain. To rationalize the LCST behavior, we calculate the ζ-potential that shows charge inversion of the protein for solutions containing multivalent ions. The ζ-potential increases with T. Performing simulations of two BSA proteins, we demonstrate that the protein-protein binding is mediated by multiple cation bridges and involves similar dehydration effects that cause a large entropy gain which more than compensates for rotational and translational entropy losses of the proteins. Thus, the LCST behavior is entropy-driven, but the associated solvation effects are markedly different from hydrophobic hydration. Our findings have direct implications for tuning the phase behavior of biological and soft-matter systems, e.g., protein condensation and crystallization.

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.

Tunable lattice thermal conductivity of twisted bilayer MoS2.

We have studied the thermal conductivity (κ) of layered MoS2, a typical member of the transition metal dichalcogenide (TMDC) materials, using fully atomistic molecular dynamics simulations and Boltzmann transport equation (BTE) based first principles methods. We investigate the tuning of the thermal conductivity with the twist angle between two layers and found a decreasing trend of κ with the increase in the lattice constant of the moiré superlattice. The thermal conductivity at twist angle θ = 21.78° is found to be 72.03 W m-1 K-1 and for an angle of 2.87°, it reaches 54.48 W m-1 K-1, leading to a 32% reduction in the thermal conductivity. We use first principles calculations based on the BTE for phonons to give a microscopic origin of the decrease in thermal conductivity through anharmonic phonon scattering events and also reaffirm the MD simulation results for the monolayer and bilayer.

Ultra-high permeable phenine nanotube membranes for water desalination.

Nanopore desalination technology hinges on high water-permeable membranes which, at the same time, block ions efficiently. In this study, we consider a recently synthesized [Science363, 151-155 (2019)] phenine nanotube (PNT) for water desalination applications. Using both equilibrium and non-equilibrium molecular dynamics simulations, we show that the PNT membrane completely rejects salts, but permeates water at a rate which is an order-of-magnitude higher than that of all the membranes used for water filtration. We provide the microscopic mechanisms of salt rejection and fast water-transport by calculating the free-energy landscapes and electrostatic potential profiles. A collective diffusion model accurately predicts the water permeability obtained from the simulations over a wide range of pressure gradients. We propose a method to calculate the osmotic water permeability from the equilibrium simulation data and find that it is very high for the PNT membrane. These remarkable properties of PNT can be applied in various nanofluidic applications, such as ion-selective channels, ionic transistors, sensing, molecular sieving, and blue energy harvesting.

Thermodynamics and its correlation with dynamics in a mean-field model and pinned systems: A comparative study using two different methods of entropy calculation.

A recent study introduced a novel mean-field model system where each particle over and above the interaction with its regular neighbors interacts with k extra pseudo-neighbors. Here, we present an extensive study of thermodynamics and its correlation with the dynamics of this system. We surprisingly find that the well-known thermodynamic integration (TI) method of calculating the entropy provides unphysical results. It predicts vanishing of the configurational entropy at temperatures close to the onset temperature of the system and negative values of the configurational entropy at lower temperatures. Interestingly, well below the temperature at which the configurational entropy vanishes, both the collective and the single-particle dynamics of the system show complete relaxation. Negative values of the configurational entropy are unphysical, and complete relaxation when the configurational entropy is zero violates the prediction of the random first-order transition theory (RFOT). However, the entropy calculated using the two-phase thermodynamics (2PT) method remains positive at all temperatures for which we can equilibrate the system, and its values are consistent with RFOT predictions. We find that with an increase in k, the difference in the entropy computed using the two methods increases. A similar effect is also observed for a system where a randomly selected fraction of the particles are pinned in their positions in the equilibrated liquid. We show that the difference in entropy calculated via the 2PT and TI methods increases with pinning density.

Quantum Circuit Rules for Molecular Electronic Systems: Where Are We Headed Based on the Current Understanding of Quantum Interference, Thermoelectric, and Molecular Spintronics Phenomena?

In this minireview, we discuss important aspects of the various quantum phenomena (such as quantum interference, spin-dependent charge transport, and thermoelectric effects) relevant in single-molecule charge transport and list some of the basic circuit rules devised for different molecular systems. These quantum phenomena, in conjunction with the existing empirical circuit rules, can help in predicting some of the structure-property relationships in molecular circuits. However, a universal circuit law that predicts the charge transport properties of a molecular circuit has not been derived yet. Having such law(s) will help to design and build a complex molecular device leading to exciting unique applications that are not possible with the traditional silicon-based technologies. Based on the existing knowledge in the literature, here we open the discussion on the possible future research directions for deriving unified circuit law(s) to predict the charge transport in complex single-molecule circuits.

Insight into the Mechanism of Carrier-Mediated Delivery of siRNA in the Cell Membrane Using MD Simulation.

The effective translocation of small interfering RNA (siRNA) across cell membranes has become one of the main challenges in gene silencing therapy. In this study, we have carried out molecular dynamics simulations to investigate a systematic procedure with different carriers that could be convenient for efficient siRNA delivery into the cell. Starting with poly-amido-amine (PAMAM) dendrimers and cholesterol molecules as carriers, we have found cholesterol as the most efficient carrier for siRNA when it is covalently attached with the siRNA terminal group. Our simulations show that binding of this complex in the lipid membrane alters the structure and dynamics of the nearby lipids to initiate the translocation process. Potential of mean force (PMF) was computed for siRNA with the carriers along the bilayer normal to understand the spontaneity of the process. Though all the PMF profiles show repulsive interaction inside the bilayer, the siRNA with cholesterol shows a comparative attractive interaction (∼27 kcal/mol) with respect to the siRNA-PAMAM complex. Altogether, our results demonstrate the binding interaction of the siRNA-carrier complex in the lipid membrane and propose a theoretical model for the efficient carrier by comparative study of the binding. The probable mechanism of the translocation process is also provided by the alteration of the lipid structure and dynamics for specifically siRNA-cholesterol binding.

Predicting the DNA Conductance Using a Deep Feedforward Neural Network Model.

Double-stranded DNA (dsDNA) has been established as an efficient medium for charge migration, bringing it to the forefront of the field of molecular electronics and biological research. The charge migration rate is controlled by the electronic couplings between the two nucleobases of DNA/RNA. These electronic couplings strongly depend on the intermolecular geometry and orientation. Estimating these electronic couplings for all the possible relative geometries of molecules using the computationally demanding first-principles calculations requires a lot of time and computational resources. In this article, we present a machine learning (ML)-based model to calculate the electronic coupling between any two bases of dsDNA/dsRNA and bypass the computationally expensive first-principles calculations. Using the Coulomb matrix representation which encodes the atomic identities and coordinates of the DNA base pairs to prepare the input dataset, we train a feedforward neural network model. Our neural network (NN) model can predict the electronic couplings between dsDNA base pairs with any structural orientation with a mean absolute error (MAE) of less than 0.014 eV. We further use the NN-predicted electronic coupling values to compute the dsDNA/dsRNA conductance.

Concerted Interactions between Multiple gp41 Trimers and the Target Cell Lipidome May Be Required for HIV-1 Entry.

The HIV-1 envelope glycoprotein gp41 mediates the fusion between viral and host cell membranes leading to virus entry and target cell infection. Despite years of research, important aspects of this process such as the number of gp41 trimers involved and how they orchestrate the rearrangement of the lipids in the apposed membranes along the fusion pathway remain obscure. To elucidate these molecular underpinnings, we performed coarse-grained molecular dynamics simulations of HIV-1 virions pinned to the CD4 T cell membrane by different numbers of gp41 trimers. We built realistic cell and viral membranes by mimicking their respective lipid compositions. We found that a single gp41 was inadequate for mediating fusion. Lipid mixing between membranes, indicating the onset of fusion, was efficient when three or more gp41 trimers pinned the membranes. The gp41 trimers interacted strongly with many different lipids in the host cell membrane, triggering lipid configurational rearrangements, exchange, and mixing. Simpler membranes, comprising fewer lipid types, displayed strong resistance to fusion, revealing the crucial role of the lipidomes in HIV-1 entry. Performing simulations at different temperatures, we estimated the free energy barrier to lipid mixing, and hence membrane stalk formation, with three and four tethering gp41 trimers to be ∼6.2 kcal/mol, a >4-fold reduction over estimates without gp41. Together, these findings present molecular-level, quantitative insights into the early stages of gp41-mediated HIV-1 entry. Preventing the requisite gp41 molecules from tethering the membranes or altering membrane lipid compositions may be potential intervention strategies.