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In the interstellar medium, several complex organic molecules are found, and of these molecules, methanol is the simplest and the most ubiquitous one. By comparing the observed infrared (IR) spectra from astrochemical data, with laboratory experiments, one can deduce the composition and structure of these astrochemical ices. Computational studies are scarce, yet they could be greatly helpful in understanding the nature of these molecules. On that premise, the present study reports a molecular dynamics study of adsorbed methanol on the KBr substrate at 90 K and 130 K. After validating the potential parameters, two adsorbed phases differing in their thickness along the z-axis: 4 × 10 × 4 (4 layers) and 4 × 10 × 50 (50 layers) were simulated. Depending on this thickness, the IR spectra and density distribution functions were computed for the bottom and top 10 Å of the 4 layers of adsorbed methanol and the top, middle, and bottom 10 Å of the 50 layers of adsorbed methanol on the KBr substrate. The bottom 10 Å of the adsorbed phase exhibit considerable disorder. Additionally, the bands in the IR spectra of these bottom 10 Å show widening, referring to a heterogeneous environment. It is further reported that the slower heating and cooling of the adsorbed phase between 90 K and 130 K leads to a complete reversal of the changes seen in heating. Our findings here further clarify the recent observation of the amorphous phase of different astrochemical molecules seen at low temperatures and their crystalline phase seen at relatively higher temperatures.

We present the self-assembly of DNA nanostars having three, four and five arms into a gel phase using a bead-spring coarse-grained model.

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.

The fast flow rate of water through nanochannels has promising applications in desalination, energy conversion, and nanomedicine. We have used molecular dynamics simulations to show that the water molecules passing through a wide single-walled carbon nanotube (CNT) cavity get aligned by flow to have a net dipole moment along the flow direction. With increasing flow velocity, the net dipole moment first increases and eventually saturates to a constant value. This behavior is similar to the Langevin theory of paraelectricity with the flow velocity acting as an effective aligning field. We show conclusively that the microscopic origin of this behavior is the preferential entry of water molecules with their dipole vectors pointing inward along the CNT axis., 5 pages, 4 figures

The oxidative damage of DNA is a compelling issue in molecular biophysics as it plays a vital role in the epigenetic control of gene expression and is believed to be associated with mutagenesis, carcinogenesis, and ageing. To understand the microscopic structural changes in physical properties of DNA and the resulting influence on its function due to oxidative damage of its nucleotide bases, we have conducted all-atom molecular dynamic simulations of double-stranded DNA (dsDNA) with its guanine bases being oxidized. The guanine bases are more prone to oxidative damage due to the lowest value of redox potential among all nucleobases. We have analyzed the local as well as global mechanical properties of native and oxidized dsDNA and explained those results by microscopic structural parameters and thermodynamic calculations. Our results show that the oxidative damage of dsDNA does not deform the Watson-Crick geometry; instead, the oxidized DNA structures are found to be better stabilized through electrostatic interactions. Moreover, oxidative damage changes the mechanical, helical, and groove parameters of dsDNA. The persistence length, stretch modulus, and torsional stiffness are found to be 48.87 nm, 1239.26 pN, and 477.30 pN.nm^2, respectively, for native dsDNA, and these values are 61.31 nm, 659.91 pN, and 407.79 pN.nm^2, respectively, when all the guanine bases of the dsDNA are oxidized. Compared to the global mechanical properties, the changes in helical and groove properties are found to be more prominent, concentrated locally at the oxidation sites, and causing the transition of the backbone conformations from BI to BII at the regions of oxidative damage.

Peptide nucleic acids (PNAs) are charge-neutral polyamide oligomers having extremely favorable thermal stability and high affinity to cell membranes when coupled with cationic cell-penetrating peptides (CPPs), as well as the encouraging antisense and antigene activity in cell-free systems. The study of the mechanical properties of short PNA molecules is rare both in experiments and theoretical calculations. Here, we studied the microscopic structures and elastic properties; namely, persistence length, stretch modulus, twist-stretch coupling, and structural crookedness of double-stranded PNA (dsPNA) and their hybrid derivatives using all-atom MD simulation and compared them with those of double-stranded DNA (dsDNA) and double-stranded RNA (dsRNA). The stretch modulus of the dsPNA is found to be ∼160 pN, an order of magnitude lower than that of dsDNA and smaller than dsRNA, respectively. Similarly, the persistence length of dsPNA is found to be ∼35 nm, significantly smaller than those of dsDNA and dsRNA. The PNA-DNA and PNA-RNA hybrid duplexes have elastic properties lying between that of dsPNA and dsDNA/dsRNA. We argue that the neutral backbones of the PNA make it less stiff than dsDNA and dsRNA molecules. Measurement of structural crookedness and principal component analysis additionally support the bending flexibility of dsPNA. Detailed analysis of the helical-rise coupled to helical-twist indicates that the PNA-DNA hybrid over-winds like dsDNA, while PNA-PNA and PNA-RNA unwind like dsRNA upon stretching. Because of the highly flexible nature of PNA, it can bind other biomolecules by adopting a wide range of conformations and is believed to be crucial for future nanobiotechnology research studies.

The diminishing trend of lattice thermal conductivity with (κ) with the Moiré lattice constant of twisted bilayer MoS2.

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, CaCl_2, MgCl_2, and YCl_3) 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 {\zeta}-potential that shows charge inversion of the protein for solutions containing multivalent ions. The {\zeta}-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.

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 Sr

Using molecular dynamics simulations, we report phase separation in a 50:50 mixture of hot(active) and cold(passive) dumbbells which interact by Lennard-Jones potential. The ratio of the temperature difference between hot and cold dumbbells to the temperature of cold dumbbells is a measure of the activity $\chi$ of the system. From constant density simulations, we observe that the hot and cold dumbbells phase separate at high activity ratio ($\chi > 5.80$). The critical activity of dumbbells is higher compared to that of a mixture of hot and cold Lennard-Jones monomers ($\chi > 3.44$). The extent of phase separation is greater for high density. As activity increases, the cold dumbbells cohere to form a large cluster indicating increased phase separation which is quantified by an order parameter. On phase separation, the effective volume of the hot dumbbells increases which leads to the increase in their entropy which is calculated by two-phase thermodynamic(2PT) method. Also, the phase separation pushes the cold dumbbells to form a dense cluster which develops crystalline order with pre-dominantly FCC and HCP packing, but the individual dumbbells have random orientations. The high kinetic pressure of hot dumbbells is balanced by the virial pressure of cold dumbbells. The simulation of the non-equilibrium system at different ratios of number of hot dumbbells to cold dumbbells reveals that the critical activity decreases with increase in fraction of hot dumbbells., Comment: 12 pages, 16 figures

Graphene nanoslit pore is used for nanofluidic devices like 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 model, our simulations reveal the independence of equilibrium number density $(n \sim 13 nm^{-2})$ for SPC/E and $(n \sim 11.5 nm^{-2})$ for TIP4P/2005) across twists. Based on the respective densities of water models, the structure and dielectric constant are invariant of twist angles. The confined water structure at this shows square ice ordering for SPC/E water only. TIP4P/2005 shows ordering at the vicinity of a critical density $(n \sim 12.5 nm^{-2})$. The average perpendicular dielectric constant of the confined water remains anomalously low ($\sim 2$ for SPC/E and $\sim 6$ for TIP4P/2005) for 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 $5.1^{o}$. Our results indicate that small angular misalignment will not impair the dielectric properties of monolayer water within graphene slit-pore but can significantly influence its dynamics., 29 pages, 12 figures

Increasing the energy density in electric double-layer capacitors (EDLCs), also known as supercapacitors, remains an active area of research. Specifically, there is a need to design and discover electrode and electrolyte materials with enhanced electrochemical storage capacity. Here, using fully atomistic molecular dynamics (MD) simulations, we investigate the performance of hyper-branched “poly(amidoamine) (PAMAM)” dendrimer as an electrolyte and an electrode coating material in a graphene-based supercapacitor. We investigate the performance of the capacitor using two different modeling approaches, namely the constant charge method (CCM) and the constant potential method (CPM). These simulations facilitated the direct calculation of the charge density, electrostatic potential, and field, and hence the differential capacitance. We found that the presence of the dendrimer in the electrodes and the electrolyte increased the capacitance by about 65.25% and 99.15%, respectively, compared with the bare graphene electrode-based aqueous EDLCs. Further analysis revealed that these increases were due to the enhanced electrostatic screening and reorganization of the double-layer structure of the dendrimer-based electrolyte., TM thanks MoE, India, for financial support in the form of scholarship. We also acknowledge computational support through TUE-CMS, IISc funded by DST, India. We also thank Supercomputer Education and Research Center (SERC), IISc, for providing supercomputer time at CRAY, SAHASRAT machine. PKM acknowledges funding through SERB, IRHPA (No.IPA/2020/000034).

Packaging paternal genome into tiny sperm nuclei during spermatogenesis requires 10sup6/sup-fold compaction of DNA, corresponding to a 10-20 times higher compaction than in somatic cells. While such a high level of compaction involves protamine, a small arginine-rich basic protein, the precise mechanism at play is still unclear. Effective pair potential calculations and large-scale molecular dynamics simulations using a simple idealized model incorporating solely electrostatic and steric interactions clearly demonstrate a reversible control on DNA condensates formation by varying the protamine-to-DNA ratio. Microscopic states and condensate structures occurring in semidilute solutions of short DNA fragments are in good agreement with experimental phase diagram and cryoTEM observations. The reversible microscopic mechanisms induced by protamination modulation should provide valuable information to improve a mechanistic understanding of early and intermediate stages of spermatogenesis where an interplay between condensation and liquid-liquid phase separation triggered by protamine expression and post-translational regulation might occur. Moreover, recent vaccines to prevent virus infections and cancers using protamine as a packaging and depackaging agent might be fine-tuned for improved efficiency using a protamination control.

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 is rescued by host antibodies targeting HIV-1. Understanding the molecular mechanism of this rescue would be important to develop and improve antibody-based therapies. 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, to unravel the underlying mechanisms. We find that the Q563R mutation, which the entrydeficient 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 again 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 arising against specific antibodies.

"Pink" or 1/f noise is a natural phenomenon omnipresent in physics, economics, astrophysics, biology, and even music and languages. In electrophysiology, the stochastic activity of a number of biological ion channels and artificial nanopores could be characterized by current noise with a 1/f power spectral density. In the anthrax toxin channel (PA63), it appears as fast voltage-independent current interruptions between conducting and nonconducting states. This behavior hampers potential development of PA63 as an ion-channel biosensor. On the bright side, the PA63 flickering represents a mesmerizing phenomenon to investigate. Notably, similar 1/f fluctuations are observed in the channel-forming components of clostridial binary C2 and iota toxins, which share functional and structural similarities with the anthrax toxin channel. Similar to PA63, they are evolved to translocate the enzymatic components of the toxins into the cytosol. Here, using high-resolution single-channel lipid bilayer experiments and all-atom molecular dynamic simulations, we suggest that the 1/f noise in PA63 occurs as a result of "hydrophobic gating" at the ϕ-clamp region, the phenomenon earlier observed in several water-filled channels "fastened" inside by the hydrophobic belts. The ϕ-clamp is a narrow "hydrophobic ring" in the PA63 lumen formed by seven or eight phenylalanine residues at position 427, conserved in the C2 and iota toxin channels, which catalyzes protein translocation. Notably, the 1/f noise remains undetected in the F427A PA63 mutant. This finding can elucidate the functional purpose of 1/f noise and its possible role in the transport of the enzymatic components of binary toxins.

In experimental research-driven biomaterials science, the influence of different material properties (elastic stiffness, surface energy, etc.) and, to a relatively lesser extent, biophysical stimulation (electric/magnetic) on cell-material interactions has been extensively investigated. Despite the central importance of protein adsorption on cell-material interactions, the quantitative analysis to probe into the role of physicochemical factors in protein adsorption remains largely unexplored in biomaterials science. In recent studies, the critical role of electric field stimulation toward the modulation of cell functionality in implantable biomaterials has been experimentally demonstrated. Given this background, we investigated the influence of external electric field stimulation (upto 1.00 V/nm) on fibronectin (FN) adsorption on a hydroxyapatite (HA) (001) surface at 300 K using the all-atom molecular dynamics (MD) simulation method. FN adsorption was found to be governed by attractive electrostatic interactions, which changed with the electric field strength. Nonmonotonous changes in the structural integrity of FN were recorded with the change in the field strength and direction. This can be attributed to the spatial rearrangement of the positions of local charges and the global structural changes of proteins. The dipole moment vectors of FN, water, and HA quantitatively exhibited a similar pattern of orienting themselves parallel to the field direction, with field strength-dependent increase in their magnitudes. No significant change has been recorded for the radial distribution function of water surrounding FN. Field-dependent variation in the salt bridge nets and the number of hydrogen bonds between FN and HA were also examined. One of the important results in the context of cell-material interaction is that the RGD (Arg-Gly-Asp) sequence of FN was exposed to the solvent side when the field was applied along an outward direction perpendicular to the HA (001) surface. In summary, the present study provides molecular insights into the influence of electric field stimulation on phenomenological interactions involved in FN adsorption on the HA surface. © 2020 American Chemical Society. All rights reserved.

The separation of linear from branched hydrocarbons is often required in many situations. There are several methods through which they can be separated but none provides a very high degree of purity or works without considerable expenditure of energy. Recently, a novel method was proposed to separate a mixture of neopentane and n-pentane. The present work demonstrates that the method can be used for separating other mixtures of hydrocarbons as well, by attempting the separation of a mixture of 2,2-dimethyl butane and n-pentane. Intermolecular interaction potentials have been modified to reproduce the experimental heat of adsorption and diffusivity of 2,2-dimethyl butane and n-pentane in zeolite NaY. The method involves choosing the correct host zeolite or other porous solids and introducing hot zones at appropriate positions. This result drives both the components to the opposite ends of the zeolite column, thus leading to separation. The achieved separation factors are much higher than what can be obtained with the help of existing methods. Different properties have been computed to understand the process involved in the separation of the mixture. The approach employed here uses very little energy for separation, making it suitable for green chemistry.

In this work, we report a novel strategy to construct molecular diodes with a record tunable rectification ratio of as high as 10^6 using oxidatively damaged DNA molecules. Being exposed to several endogenous and exogenous events, DNA suffers constant oxidative damages leading to 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 of 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 CT 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 fully oxidized Drew-Dickerson sequence. The presence of 8oxoG guanine leads to the trapping of charge, thus operates as a charge sink, which reveals how oxidized guanine saves the rest of the genome from further oxidative damage.

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., 13 pages, 15 figures

Cost-effective, fast, and reliable DNA sequencing can be enabled by advances in nanopore-based methods, such as the use of atomically thin graphene membranes. However, strong interaction of DNA bases with graphene leads to undesirable effects such as sticking of DNA strands to the membrane surface. While surface functionalization is one way to counter this problem, here, we present another solution based on a heterostructure nanopore system, consisting of a monolayer of graphene and hexagonal boron nitride (hBN) each. Molecular dynamics studies of DNA translocation through this heterostructure nanopore revealed a surprising and crucial influence of the heterostructure layer order in controlling the base specific signal variability. Specifically, the heterostructure with graphene on top of hBN had nearly 3-10× lower signal variability than the one with hBN on top of graphene. Simulations point to the role of differential underside sticking of DNA bases as a possible reason for the observed influence of the layer order. Our studies can guide the development of experimental systems to study and exploit DNA translocation through two-dimensional heterostructure nanopores for single molecule sequencing and sensing applications.

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.

The DNA molecule, apart from carrying the genetic information, plays a crucial role in a variety of biological processes and find applications in drug design, nanotechnology and nanoelectronics. The molecule undergoes significant structural transitions under the influence of forces due to physiological and non-physiological environments. Here, we summarize the insights gained from simulations and single-molecule experiments on the structural transitions and mechanics of DNA under force, as well as its elastic properties, in various environmental conditions, and discuss appealing future directions., Review Article, Accepted for publication in Current Opinion in Structural Biology

Functionalizing graphene with polymers is an important area of research, owing to the potential applications of graphene in biomedicine and nanotechnology. In this paper, we investigate the covalen...

A new computational framework based on multiscale modeling approach is developed to calculate the current–voltage (V–I) characteristics of a double stranded DNA (dsDNA) attached between two gold el...

Pore forming toxins (PFTs) are proteins which form unregulated oligomeric pores on target plasma membranes to cause ion leakage and cell death and represent the largest class of bacterial virulence factors. With increasing antibiotic-resistant bacterial strains, alternate therapies are being developed to target toxin pore formation rather than the bacteria themselves. One strategy is to undermine the stability of these multimeric pores, whose subunits are held together by complex amino acid interaction networks, by identifying key residues in these networks which could be plausible drug or mutagenesis targets. However, this requires a quantitative assessment of per residue contributions towards pore stability, which cannot be reliably gleaned from static crystal/cryo-EM pore structures. In this study, we overcome this limitation by developing a computational screening algorithm that employs fully atomistic molecular dynamics simulations coupled with energy-based screening that can predict 'hot-spot' residues which engage in persistent and stabilizing hydrogen bonds or salt bridges across protein-protein interfaces. Application of this algorithm to prototypical

Several analytical calculations and computer simulations propose that cylindrical monodispersive rods having an aspect ratio (ratio of length to diameter) greater than 4 can exhibit liquid crystal (LC) ordering. But, recent experiments demonstrated the signature of LC ordering in systems of 4- to 20-base pair (bp) long nucleic acids (NAs) that do not satisfy the shape anisotropy criterion. Mechanisms of end-to-end adhesion and stacking have been proposed to explain this phenomenon. In this study, using all-atom molecular dynamics (MD) simulation, we explicitly verify the end-to-end stacking of double-stranded RNA (dsRNA) and demonstrate the LC ordering at the microscopic level. Using umbrella sampling (US) calculation, we quantify the potential of mean force (PMF) between two dsRNAs for various reaction coordinates (RCs) and compare our results with previously reported PMFs for double-stranded DNA (dsDNA). The PMF profiles demonstrate the anisotropic nature of inter-NA interaction. We find that, like dsDNA, dsRNA also prefers to stack on top of each other while repelling sideways, leading to the formation of supra-molecular-columns that undergo LC ordering at high NA volume fraction (φ). We also demonstrate and quantify the nematic ordering of the RNAs using several hundred nanosecond-long MD simulations that remain almost invariant for different initial configurations and under different external physiological conditions.

In this study, we compare the charge transport properties of multiple double-stranded (ds)RNA sequences with corresponding dsDNA sequences. Recent studies have presented a contradictory picture of relative charge transport efficiencies in A-form DNA : RNA hybrids and dsDNA. Using a multiscale modelling framework, we compute conductance of dsDNA and dsRNA using Landauer formalism in the coherent limit and Marcus-Hush theory in the incoherent limit. We find that dsDNA conducts better than dsRNA in both the charge transport regimes. Our analysis shows that the structural differences in the twist angle and slide of dsDNA and dsRNA are the main reasons behind the higher conductance of dsDNA in the incoherent hopping regime. In the coherent limit however, for the same base pair length, the conductance of dsRNA is higher than that of dsDNA for the morphologies where dsRNA has a smaller end-to-end length relative to that of dsDNA.

Recently, some of us developed a novel model glass-forming liquid with k extra interactions with pseudo neighbours to each liquid particle over and above the regular interactions with its neighbours. Analysis of the structure and dynamics of these systems showed that with an increase in k the systems have more mean-field like properties. This work presents an extensive study of the thermodynamics of the above-mentioned model for several values of k and its correlation with the dynamics. We surprisingly find that the usual thermodynamic integration (TI) method of calculating the entropy provides unphysical results for this model. It predicts the vanishing of configurational entropy at state points at which both the collective and the single-particle dynamics of the system show complete relaxation. We then employ a new method known as the two-phase thermodynamics (2PT) method to calculate the entropy. We find that with an increase in k the difference in the entropy computed using the two methods (2PT and TI) increases. We also find that in the temperature range studied, the entropy calculated via the 2PT method satisfies the Adam-Gibbs (AG) relationship between the relaxation time and the configurational entropy, whereas the entropy calculated via the TI method shows a strong violation of the same. We then apply the 2PT method to calculate the entropy in another system where some fractions of particles are pinned randomly in their equilibrium positions. This system also shows a similar breakdown of the AG relationship as reported earlier. We show that the difference in entropy calculated via the 2PT and TI methods increases with an increase in pinning density. We also find that when the entropy is calculated using the 2PT method, the AG relationship between the dynamics and the entropy holds., Comment: 16 pages, 27 figures, 3 tables

The proton dynamics of a 2D water monolayer confined inside a graphene slit pore is studied in Cartesian and molecular frames of reference using molecular dynamics simulations. The vibrational density of states of the proton was calculated versus temperature and was further used to deduce the mean kinetic energy of the hydrogen atoms, Ke(H), in both frames of reference. The directional components of Ke(H) are in good agreement with experimental observations for bulk as well as nanoconfined water. Nonetheless, while in the molecular frame of reference the effect of temperature on the anisotropy ratios of Ke(H) (the ratio between its directional components) are practically invariant between the 2D and 3D cases, those in the Cartesian frame of reference reveal a rather notable reduction across 200 K, indicating the occurrence of an order-disorder transition. This result is further supported by the calculated entropy and enthalpy of the confined water molecules. Overall, it is shown that Ke(H) anisotropy ratios may serve as a valuable order parameter for detecting structural transformations in hydrogen bonds containing molecular systems.

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 [Science 363, 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., Comment: 23 pages, 5 figures

DNA has emerged as one of the smartest biopolymers to bridge the gap between chemical science and biology to design scaffolds like hydrogels by physical entanglement or chemical bonding with remarkable properties. We present here a completely new application of DNA-based hydrogels in terms of their capacity to stimulate membrane endocytosis, leading to enhanced cell spreading and invasion for cells in ex vivo 3D spheroids models. Multiscale simulation studies along with DLS data showed that the hydrogel formation was enhanced at lower temperature and it converts to liquid with increase in temperature. DNA hydrogels induced cell spreading as observed by the increase in cellular area by almost two-fold followed by an increase in the receptor expression, the endocytosis, and the 3D invasion potential of migrating cells. Our first results lay the foundation for upcoming diverse applications of hydrogels to probe and program various cellular and physiological processes that can have lasting applications in stem cell programming and regenerative therapeutics.

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.

Protein adsorption is the first key step in cell-material interaction. The initial phase of such adsorption process can only be probed using modelling approaches like molecular dynamics (MD) simulation. Despite a large number of studies on the adsorption behaviour of proteins on different biomaterials including hydroxyapatite (HA); little attention has been paid towards quantitative assessment of the effects of various physicochemical influencers like surface modification, pH, and ionic strength. Among these factors, surface modification through isomorphic substitution of foreign ions inside the apatite structure is of particular interest in the context of protein-HA interaction as it is widely used to tailor the biological response of HA. Given this background, we present here the molecular-level understanding of fibronectin (FN) adsorption mechanism and kinetics on Sr2+-doped HA (001) surface, at 300K by means of all-atom molecular dynamics simulation. Electrostatic interaction involved in adsorption of FN on HA was found to be significantly modified in presence of Sr2+ doping in apatite lattice. In harmony with the published experimental observations, the Sr-doped surface was found to better support FN adhesion compared to pure HA, with 10 mol% Sr-doped HA exhibiting best FN adsorption. 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 no. 20-44, 74-88) of the FN module. Rupture forces to disentangle FN from the biomaterials 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 RGD motif for the interaction with cell surface receptor integrin is not significantly influenced by Sr2+ substitution. Summarizing, the present work establishes a quantitative foundation towards the molecular basis of the earlier experimentally validated better cytocompatibility of Sr-doped HA.

Some recent SARS-CoV-2 variants appear to have increased transmissibility than the original strain. An underlying mechanism could be the improved ability of the variants to bind receptors on target cells and infect them. In this study, we provide atomic-level insight into the binding of the receptor binding domain (RBD) of the wild-type SARS-CoV-2 spike protein and its single (N501Y), double (E484Q, L452R) and triple (N501Y, E484Q, L452R) mutated variants to the human ACE2 receptor. Using extensive all-atom molecular dynamics simulations and advanced free energy calculations, we estimate the associated binding affinities and binding hotspots. We observe significant secondary structural changes in the RBD of the mutants, which lead to different binding affinities. We find higher binding affinities of the double (E484Q, L452R) and triple (N501Y, E484Q, L452R) mutated variants than the wild type and the N501Y variant, which could contribute to the higher transmissibility of recent variants containing these mutations.

The separation of linear from branched hydrocarbons is often required in many situations. There are several methods through which they can be separated but none provides a very high degree of purity or works without considerable expenditure of energy. Recently, a novel method was proposed to separate a mixture of neopentane and n-pentane. The present work demonstrates that the method can be used for separating other mixtures of hydrocarbons as well, by attempting the separation of a mixture of 2,2-dimethyl butane and n-pentane. Intermolecular interaction potentials have been modified to reproduce the experimental heat of adsorption and diffusivity of 2,2-dimethyl butane and n-pentane in zeolite NaY. The method involves choosing the correct host zeolite or other porous solids and introducing hot zones at appropriate positions. This result drives both the components to the opposite ends of the zeolite column, thus leading to separation. The achieved separation factors are much higher than what can be obtained with the help of existing methods. Different properties have been computed to understand the process involved in the separation of the mixture. The approach employed here uses very little energy for separation, making it suitable for green chemistry.

DNA has emerged as one of the smartest biopolymers to bridge the gap between chemical science and biology to design scaffolds like hydrogels by physical entanglement or chemical bonding with remarkable properties. We present here a completely new application of DNA based hydrogels in terms of their capacity to stimulate membrane endocytosis, leading to enhanced cell spreading and invasion for cells in ex-vivo 3D spheroids models. Multiscale simulation studies along with DLS data showed that the hydrogel formation was enhanced at lower temperature and it converts to liquid with increase in temperature. DNA hydrogels induced cell spreading as observed by increase in cellular area by almost two-folds followed by increase in receptor expression, endocytosis and 3D invasion potential of migrating cells. Our first results lay the foundation for upcoming diverse applications of hydrogels to probe and program various cellular and physiological processes that can have lasting applications in stem cells programming and regenerative therapeutics.

We report equilibrium and nonequilibrium molecular dynamics (MD) simulations of two nucleosome core particles (NCPs) stacked with their dyad axes oriented in parallel or antiparallel fashion. From the equilibrium trajectories, we determine the bridging behavior of different histone tails and observe that different sets of histone tails play important roles in the two orientations in stabilizing the NCP stack. While the H4 and H2A tails play important intermediary roles in the parallel stack, the H3 and H2B tails are important in the antiparallel stack. We use steered MD simulations to unstack the two NCPs and find a stark difference in their unstacking pathways. While the average rupture force was found to be higher for the parallel stack, the work done for complete unstacking was similar for both orientations. We use Jarzynski equality to determine the PMF profiles along the unstacking pathway, relate our findings to the behavior of NCP mesophases, and derive insights into the enigmatic nucleosomal organization in the chromatin fiber.