Comparative Molecular Dynamics Study Research Articles

Fluorinated [2]rotaxanes as sensitive 19F MRI agents: Threading for higher sensitivity

As a promising imaging technology, the low sensitivity of fluorine-19 magnetic resonance imaging (19F MRI) severely hinders its biomedical applications. Herein, we have developed an unprecedented rotaxane-based strategy to improve the sensitivity of 19F MRI agents. By threading the fluorinated macrocycle into 2-blade pinwheel [2]rotaxanes, the 19F longitudinal relaxation rate R1 was dramatically increased, resulting in a significant 19F MRI signal intensity enhancement of up to 79%. Through comparative molecular dynamics studies using a series of solution and solid-state 1H/19F nuclear magnetic resonance (1H/19F NMR) and molecular dynamics simulations, it was found that the formation of mechanical bonds dramatically restricts the motion of the wheel fluorines and thus increasing the R1 for higher 19F MRI sensitivity. Besides a novel strategy for improving 19F MRI sensitivity, this study has established 19F NMR/MRI as a valuable technology for monitoring the molecular dynamics of rotaxanes, which may shed new light on high-performance 19F MRI agents and molecular devices.

Comparative docking and molecular dynamics studies of molnupiravir (EIDD-2801): implications for novel mechanisms of action on influenza and SARS-CoV-2 protein targets

Molnupiravir (EIDD-2801) (MLN) is an oral antiviral drug for COVID-19 treatment, being integrated into viral RNA through RNA-dependent RNA polymerase (RdRp). Upon ingestion, MLN is transformed into two active metabolites: β-d-N4-hydroxycytidine (NHC) (EIDD-1931) in the host plasma, and EIDD-1931-triphosphate (MTP) within the host cells. However, recent studies provide increasing evidence of MLN’s interactions with off-target proteins beyond the viral genome, suggesting that the complete mechanisms of action of MLN remain unclear. The aim of this study was therefore to investigate the molecular interactions of MLN in the form of NHC and MTP with the non-RNA structural components of avian influenza (hemagglutinin, neuraminidase) and SARS-CoV-2 (spike glycoprotein, Mpro, and RdRp) viruses and to elucidate whether these two metabolites possess the ability to form stable complexes with these major viral components. Molecular docking of NHC and MTP was performed using AutoDock 4.2.6 and the obtained protein-drug complexes were submitted to 200-ns molecular dynamics simulations in triplicate with subsequent free energy calculations using GROMACS. Docking scores, molecular dynamics and MM/GBSA results showed that MTP was tightly bound within the active site of SARS-CoV-2 RdRp and remained highly stable throughout the 200-ns simulations. Besides, it was also shown that NHC and MTP formed moderately-to-highly stable molecular complexes with off-target receptors hemagglutinin, neuraminidase and Mpro, but rather weak interactions with spike glycoprotein. Our computational findings suggest that NHC and MTP may directly inhibit these receptors, and propose that additional studies on the off-target effects of MLN, i.e. real-time protein binding assays, should be performed. Communicated by Ramaswamy H. Sarma

Comparative molecular dynamics study of liquid hydrogen annular jets in subcritical and supercritical environments

In this paper, the injection characteristics of a liquid hydrogen propellant jet under subcritical and supercritical operating conditions are comparatively studied at the molecular scale using molecular dynamics methods in the context of spacecraft propulsion systems. To control the temperature and pressure within the environment and nozzle respectively, two sub-computational domains are set up for separate modeling. The sub-computational domain merging process eliminates the broken molecular bonds by using the computational domain reduction in the x-direction. The jet velocity, density and other physical property distributions at different temperatures and pressures were comparatively studied. It is found that the rate of change of the radial density of the jet under supercritical conditions is small. Based on this, the surface area and volume of the liquid phase region of the jet were extracted and calculated. Compared to result of subcritical case, the volume of the liquid hydrogen jet in the supercritical environment is reduced by 1.9%, while the surface area is increase by 6.7%. To explain the variation in the surface area due to molecular diffusion, the molecular stress results revealed that the stress in the hydrogen jet in supercritical environment is only 88.9% of that in subcritical environment.

Comparative molecular dynamics study on the features of binding and non-binding modes of retinoic acid in cellular retinol-binding protein (I)

Retinoids play crucial roles in various biological processes by interacting with their carrier proteins such as cellular retinol-binding protein (CRBP). Understanding the molecular interactions between retinoids and CRBP enables their pharmacological and biomedical applications. Experimentally, CRBP(I) does not bind to retinoic acid, but when arginine is introduced into 108th residue instead of glutamine (Q108R), it binds to retinoic acid. Here, molecular dynamics simulations were performed to understand the differences in the microscopic and dynamic behaviors of the non-binding wild-type CRBP(I)-retinoic acid and binding Q108R variant-retinoic acid complexes. The ligand RMSD and RMSF, the binding poses of binding motif amino acids, and the number of hydrogen bonds and salt-bridges revealed the relative instability of the non-binding complex. In particular, the ligand's terminal group showed very different dynamics and interactions. So far, most studies have focused on the binding characteristics of retinoids, but the features of their non-binding modes have not been studied well. This study provides some structural insights into the non-binding modes of a retinoid in CRBP, which may be applicable in retinoid-based drug discovery and protein engineering through computational modeling.

Molecular dynamics-derived pharmacophores of Schistosoma glutathione transferase in complex with bromosulfophthalein: Screening and analysis of potential inhibitors

Schistosoma glutathione transferases (GSTs) have been identified as attractive drug targets for the design of novel antischistosomals. Here, we used in silico methods to validate the discriminative inhibitory properties of bromosulfophthalein (BSP) against the 26-kDa GST from S. japonicum (Sj26GST), and the 28-kDa GST from S. haematobium (Sh28GST), versus human GST (hGST) isoforms alpha (hGSTA), mu (hGSTM) and pi (hGSTP). The use of BSP as an archetypal selective inhibitor was harnessed to produce molecular dynamics-derived pharmacophores of the two targets. Pharmacophore-based screening using a large dataset of experimental and approved drug compounds was performed to produce a shortlist of candidates. The top candidate for each target was prioritised via molecular docking, yielding guanosine-3′-monophosphate-5′-diphosphate (G3D) for Sj26GST, and quercetin-3′-O-phosphate (Q3P) for Sh28GST. Comparative molecular dynamics studies of both candidates compared to BSP showed similar characteristics of binding stability and strength, suggesting their potential to emulate the inhibitory effects of BSP.

Improved NMR-data-compliant protein structure modeling captures context-dependent variations and expands the scope of functional inference.

Nuclear magnetic resonance (NMR) spectroscopy can reveal conformational states of a protein in physiological conditions. However, sparsely available NMR data for a protein with large degrees of freedom can introduce structural artifacts in the built models. Currently used state-of-the-art methods deriving protein structure and conformation from NMR deploy molecular dynamics (MD) coupled with simulated annealing for building models. We provide an alternate graph-based modeling approach, where we first build substructures from NMR-derived distance-geometry constraints combined in one shot to form the core structure. The remaining molecule with inadequate data is modeled using a hybrid approach respecting the observed distance-geometry constraints. One-shot structure building is rarely undertaken for large and sparse data systems, but our data-driven bottom-up approach makes this uniquely feasible by suitable partitioning of the problem. A detailed comparison of select models with state-of-art methods reveals differences in the secondary structure regions wherein the correctness of our models is confirmed by NMR data. Benchmarking of 106 protein-folds covering 38-282 length structures shows minimal experimental-constraint violations while conforming to other structure quality parameters such as the proper folding, steric clash, and torsion angle violation based on Ramachandran plot criteria. Comparative MD studies using select protein models from a state-of-art method and ours under identical experimental parameters reveal distinct conformational dynamics that could be attributed to protein structure-function. Our work is thus useful in building enhanced NMR-evidence-based models that encapsulate the contextual secondary and tertiary structure variations present during the experimentation and expand the scope of functional inference.

A Comparative Molecular Dynamics Study of Selected Point Mutations in the Shwachman-Bodian-Diamond Syndrome Protein SBDS.

The Shwachman–Diamond Syndrome (SDS) is an autosomal recessive disease whose majority of patients display mutations in a ribosome assembly protein named Shwachman–Bodian–Diamond Syndrome protein (SBDS). A specific therapy for treating this rare disease is missing, due to the lack of knowledge of the molecular mechanisms responsible for its pathogenesis. Starting from the observation that SBDS single-point mutations, localized in different domains of the proteins, are responsible for an SDS phenotype, we carried out the first comparative Molecular Dynamics simulations on three SBDS mutants, namely R19Q, R126T and I212T. The obtained 450-ns long trajectories were compared with those returned by both the open and closed forms of wild type SBDS and strongly indicated that two distinct conformations (open and closed) are both necessary for the proper SBDS function, in full agreement with recent experimental observations. Our study supports the hypothesis that the SBDS function is governed by an allosteric mechanism involving domains I and III and provides new insights into SDS pathogenesis, thus offering a possible starting point for a specific therapeutic option.

The Impact of D614G Mutation of SARS-COV-2 on the Efficacy of Anti-viral Drugs: A Comparative Molecular Docking and Molecular Dynamics Study.

D614G is one of the most reported mutations in the spike protein of SARS-COV-2 that has altered some crucial characteristics of coronaviruses, such as rate of infection and binding affinities. The binding affinity of different antiviral drugs was evaluated using rigid molecular docking. The reliability of the docking results was evaluated with the induced-fit docking method, and a better understanding of the drug-protein interactions was performed using molecular dynamics simulation. The results show that the D614G variant could change the binding affinity of antiviral drugs and spike protein remarkably. Although Cytarabine showed an appropriate interaction with the wild spike protein, Ribavirin and PMEG diphosphate exhibited a significant binding affinity to the mutated spike protein. The parameters of the ADME/T analysis showed that these drugs are suitable for further in-vitro and in-vivo investigation. D614G alteration affected the binding affinity of the RBD and its receptor on the cell surface.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00284-022-02921-6.

Thermal transport in two-dimensional carbon nitrides: A comparative molecular dynamics study

Two-dimensional (2D) carbon nitrides show a great structural diversity and have potentials in applications of thermal management and energy storage. Thus, seeking the thermal transport properties of 2D carbon nitrides is of great significance for improving the performance and reliability in practical applications. However, the experimental measurements for 2D materials are limited by various conditions, and the results of molecular dynamics (MD) simulations are quite different, e.g., the calculation results of thermal conductivity of C3N show a poor consistency. To this end, the characteristics of thermal transportation of 2D carbon-nitride nanostructures with the representatives of C3N, C2N, C3N4s(s-triazine), and C3N4t(t-triazine) are comprehensively investigated by molecular dynamics (MD) simulations using four different methods. The thermal conductivity of C3N is up to around 866Wm−1K−1 while that of C3N4t is down to around 19Wm−1K−1 in this work. Through spectral heat current (SHC) and phonon analysis, we find that the decrease of thermal conductivity for 2D carbon nitrides is due to the deterioration of out-of-plane thermal conductivity induced by regularly distributed holes and absence of CC bonds. The results show that the rate of heat tranfer in two-dimensional carbon-nitride nanostructures significantly relies on their nanostructures.

Molecular dynamics study on enhanced nucleate boiling heat transfer on nanostructured surfaces with rectangular cavities

Nanostructured surfaces have been proved to bring remarkable enhancements in nucleate boiling heat transfer, which are particularly attractive in thermal energy fields. To fully understand the effects of nano-cavities on nucleate boiling and elucidate the underlying enhanced mechanisms, a comparative molecular dynamics study on nucleate pool boiling heat transfer of liquid argon over the plain copper substrate and nanostructured substrates with different rectangular cavities is performed. The nano-cavities have the same depth of 5 nm and different widths of 3 nm, 5 nm and 8 nm. The bubble dynamics behavior on various surfaces is observed based on simulation snapshots. The results manifest that the rectangular nano-cavity can significantly reduce time and wall superheat required for the onset of nucleate boiling, as well as delay the transition from nucleation boiling regime to film boiling regime. The incipient nucleation time tin can be reduced to 990 ps from 5600 ps. Additionally, compared with the plain substrate, the rectangular nano-cavity can result in a striking decrease in boiling initiation temperature, which is up to 59 K. The underlying enhanced mechanisms are well elucidated based on the structural feature of the rectangular nano-cavity and simulation results. The liquid inside the rectangular cavity can obtain additional thermal energy from sidewalls, leading to a significant local heat accumulation effect and the heat transfer efficiency reinforcement. It is found there is a coupling enhancement effect of heat accumulation when the width of rectangular cavity is smaller. Consequently, the 3 nm wide nano-cavity can achieve maximum enhancement. These findings provide crucial evidence at the nanoscale to verify that nano-cavity can significantly enhance nucleate boiling not only by reducing nucleation time but also by decreasing the boiling initiation temperature. This study is of importance to promote further insights into the enhanced mechanism of nucleate boiling at the nanoscale and provide guidance for the performance improvement in boiling surfaces for advanced thermal energy systems.

On the propensity of formation of cyclobutane dimers in face-to-face and face-to-back uracil stacks in solution.

UV irradiation of RNA leads to the formation of intra- and inter-strand crosslinks of cyclobutane type. Despite the importance of this reaction, relatively little is known about how the mutual orientation of the two bases affects the outcome of the reaction. Here we report a comparative nonadiabatic molecular dynamics study of face-to-back (F2B) and face-to-face (F2F) stacked uracil-water clusters. The computations were performed using the second-order algebraic-diagrammatic-construction (ADC(2)) method. We found that F2B stacked uracil-water clusters either relax non-reactively to the ground state by an ethylenic twist around the CC bond or remain in the lowest nπ* state in which the two bases gradually move away from each other. This finding is consistent with the low propensity for the formation of intra-strand cyclobutane dimers between adjacent RNA bases. On the contrary, in F2F stacked uracil-water clusters, in addition to non-reactive deactivation, we found a pro-reactive deactivation pathway, which may lead to the formation of cyclobutane uracil dimers in the electronic ground state. On a qualitative level, the observed photodynamics of F2F stacked uracil-water clusters explains the greater propensity of RNA to form inter-strand cyclobutane-type crosslinks.

Study on organic molecular vibrational dynamics by TR-box-CARS spectroscopy

This paper reported a comparative study of molecular vibrational dynamics in different organic molecules by femtosecond time-resolved folded box-coherent anti-Stokes Raman scattering (TR-box-CARS) spectroscopy. As model system methanol and ethanol molecules are chosen, the coherence transfer between stretching vibration modes of C-H bonds in them are excited and detected at the same time. Different vibration periods and wavenumber spacing are found for the amplitudes of the coherent vibrations of C-H stretch modes in methanol and ethanol molecules. This study makes femtosecond TR-box-CARS possible as a prospective technique for detection and identification of organic molecular species in ambient environments. A simple spatial magic filter and frequency domain filter method with folded TR-box-CARS approach of suppressing the non-resonant FWM background is demonstrated.

Molecular mobility in bulk and in near-surface nano-layers of ultra-high-molecular-weight polyethylene

A comparative study of molecular dynamics in near-surface nanolayers and in a bulk of polyethylene is presented. Molecular mobility in near-surface nanolayers of polyethylene reactor powders and melt-crystallized films of various molecular weights prepared in different crystallization conditions were studied with the help of thermoluminescence technique using high frequency glow dicharge Ar plasma for surface activation. Molecular mobility in a bulk of the same samples was investigated by the method of radio thermoluminescence, in which a deeply penetrating γ-quanta from 60Co radiation was used for activation of the bulk. A marked difference in a temperature position of the peaks on the glow curves of plasma-induced thermoluminescence and those of radiothermoluminescence correspoding to γ- and ß-transitions was found to depend on crystallisation conditions and molecular weight. Quasi-independent segmental mobility (ß-relaxation) in the near-surface nano-layers of UHMWPE reactor powder particles synthesized at low temperatures appeared to be unexpectedly unfreezed at the temperature higher than that in the bulk. It was supposed that this happend because of crystallization under the confinement conditions during low-temperature polymerization leads to formation of a specific surface structure.

Comparative Molecular Dynamics Study of the Roles of Anion–Cation and Cation–Cation Correlation in Cation Diffusion in Li2B12H12 and LiCB11H12

Complex hydrides are potential candidates for the solid electrolyte of all-solid-state batteries owing to their high ionic conductivities in which icosahedral anion reorientational motion plays an ...

Comparative molecular dynamics study of the receptor-binding domains in SARS-CoV-2 and SARS-CoV and the effects of mutations on the binding affinity

Here, we report on a computational comparison of the receptor-binding domains (RBDs) on the spike proteins of severe respiratory syndrome coronavirus‐2 (SARS-CoV-2) and SARS-CoV in free forms and as complexes with angiotensin-converting enzyme 2 (ACE2) as their receptor in humans. The impact of 42 mutations discovered so far on the structure and thermodynamics of SARS-CoV-2 RBD was also assessed. The binding affinity of SARS-CoV-2 RBD for ACE2 is higher than that of SARS-CoV RBD. The binding of COVA2-04 antibody to SARS-CoV-2 RBD is more energetically favorable than the binding of COVA2-39, but also less favorable than the formation of SARS-CoV-2 RBD-ACE2 complex. The net charge, the dipole moment and hydrophilicity of SARS-CoV-2 RBD are higher than those of SARS-CoV RBD, producing lower solvation and surface free energies and thus lower stability. The structure of SARS-CoV-2 RBD is also more flexible and more open, with a larger solvent-accessible surface area than that of SARS-CoV RBD. Single-point mutations have a dramatic effect on distribution of charges, most prominently at the site of substitution and its immediate vicinity. These charge alterations alter the free energy landscape, while X→F mutations exhibit a stabilizing effect on the RBD structure through π stacking. F456 and W436 emerge as two key residues governing the stability and affinity of the spike protein for its ACE2 receptor. These analyses of the structural differences and the impact of mutations on different viral strains and members of the coronavirus genera are an essential aid in the development of effective therapeutic strategies. Communicated by Ramaswamy H. Sarma

Optimal loading of omecamtiv mecarbil by chitosan: A comprehensive and comparative molecular dynamics study

Biodegradable carbohydrate polymers are one of the most efficient material groups applicable in the pharmaceutical industry and medicine. In this research, the effect of chitosan chains, as a natural polymer, on the encapsulation of a myosin activator drug, omecamtiv mecarbil, was investigated by molecular dynamics (MD) simulation. The three main effective factors for loading efficiency including drug concentration (11, 46 and 91%), temperature (298.15 and 318.15 K) and the presence of water molecules (560 molecules) were considered to evaluate the polymer loading efficiency. Based on the results of 12 different systems, since the water molecules provide more effective non-covalent drug interactions than those of chitosan, the presence of molecules decreases the polymer efficiency. To obtain a molecular point of view, all possible mutual radial distribution functions were determined. The interactions between chitosan and omecamtiv mecarbil were reduced at higher temperature and in the presence of water molecules. A comprehensive and comparative insight was also discussed on the role of the three factors in changing the radius of gyration, unbonded energy profile, root-mean-square fluctuations, solvent-accessible surface area and number of hydrogen bonding. Although the same trend was not observed for the effect of drug concentration on all parameters in all systems, the higher temperature and presence of water molecules still decreased the number of loaded drugs on the polymer. Moreover, the aggregation and intra-molecular interaction of chitosan chains were reduced in the presence of water and drug molecules, so that the free active polymer sites were released to form hydrogen bonding interactions among these molecules. As a result, a type of distribution leading to the loading of the drug on polymer was observed.

Negative density-dependence of the structural relaxation time of liquid silica: insights from a comparative molecular dynamics study

In many tetrahedral network-forming liquids, structural relaxation is anomalously accelerated by compression over relatively low pressure ranges. Here, for silica, we study this problem through comparative molecular dynamics simulations using two different models. Under compression, the network structures are compacted by slight tuning of the intertetrahedral bond angles while nearly preserving the unit tetrahedral structure. The consequent structural changes are remarkable for length scales larger than the nearest neighbor ion-pair distances. Accompanying with such structural changes, the interactions of the nearest Si–O pairs remain almost unchanged, whereas those of other ion pairs are, on average, strengthened by the degree of compression. In particular, the enhancement of the net Si–O interactions at the next nearest neighbor distance, which assist an ion in escaping from the potential well, reduces the activation energy, leading to a significant acceleration of structural relaxation. The results of our comparative molecular dynamics simulations are compatible with the scenario proposed by Angell, and further indicate that the structural relaxation dynamics cannot be uniquely determined by the configurations but strongly depends on the details of the coupling between the structure and the interaction.

PEDOT:PSS nano-particles in aqueous media: A comparative experimental and molecular dynamics study of particle size, morphology and z-potential

PEDOT:PSS is the most widely used conducting polymer in organic and printed electronics. PEDOT:PSS films have been extensively studied to understand the morphology, ionic and electronic conductivity of the polymer. However, the polymer dispersion, which is used to cast or spin coat the films, is not well characterized and not well understood theoretically. Here, we study in detail the particle morphology, size, charge density and zeta potential (z-potential) by coarse-grained MD simulations and dynamic light scattering (DLS) measurements, for different pH levels and ionic strengths. The PEDOT:PSS particles were found to be 12 nm–19 nm in diameter and had a z-potential of −30 mV to −50 mV when pH was changed from 1.7 to 9, at an added NaCl concentration of 1 mM, as measured by DLS. These values changed significantly with changing pH and ionic strength of the solution. The charge density of PEDOT:PSS particles was also found to be dependent on pH and ionic strength. Besides, the distribution of different ions (PSS−, PEDOT+, Na+, Cl−) present in the solution is simulated to understand the particle morphology and molecular origin of z-potential in PEDOT:PSS dispersion. The trend in change of particle size, charge density and z- potential with changing pH and ionic strength are in good agreement between the simulations and experiments. Our results show that the molecular model developed in this work represents very well the PEDOT:PSS nano-particles in aqueous dispersion. With this study, we hope to provide new insight and an in-depth understanding of the morphology and z-potential evolution in PEDOT:PSS dispersion.

Molecular basis of the beta-lactamase protein using comparative modelling, drug screening and molecular dynamics studies to understand the resistance of β-lactam antibiotics.

Beta-lactamase (ampC) in general causes the onset of antibiotic resistance in pathogenic bacteria against the β-lactam antibiotics. Morganella morganii which belongs to the Proteae tribe of the Enterobacteriaceae family is a Gram-negative bacillus. Gram-negative bacteria are the key problematic agents among the human population in overexpressing resistance against β-lactam antibiotics. These β-lactam antibiotics being experimentally well studied still lack the key information and mechanism for their resistance. The structural information of the ampC protein is unknown and poorly studied; hence, it is the need of the hour to find effective inhibitors against it. In our study, the prediction of the three-dimensional structure of ampC protein from Morganella morganii was performed using a comparative modelling approach. The predicted structure was energetically stabilized and functional conformations were mapped through 100-ns molecular dynamics simulation runs. Also, Ramachandran plot shows the model to be stereo-chemically stable with most residues found under core allowed regions. Drug screening with several experimentally tested inhibitors was then confirmed to check the activity against ampC protein using an AutoDock tool. The results suggested OncoglabrinolC molecule as the best inhibitor (out of 21 drug molecules) with a binding affinity of - 11.44kcal/mol. Anti-bacterial/anti-parasitic inhibitors have not only been used against bacterial infections, but later reports have also shown them to work against deadly viruses such as SARS-CoV2. This key structural and inhibitory information is certain to help in the discovery of specific and potent substitute therapeutic drugs and the development of experimental procedures against human infection.

Mechanical properties of defective cyanoethynyl (2D polyaniline – C3N): A comparative molecular dynamics study versus graphene and hexagonal boron nitride

Abstract Remarkable properties that free-standing 2D nanomaterials offer have allured academic and industrial interest in them beyond graphene. One of these materials is cyanoethynyl, which is a 2D monocrystalline carbon nitride material with a C3N stoichiometry. Investigations have confirmed its high thermal stability at elevated temperatures and ferromagnetism at low temperatures, yet very little is known about its mechanical properties. This paper reports a molecular dynamics (MD) insight into this gap. The simulations are validated against density functional theory calculations. The tensile properties of defect-free C3N sheets at/under different temperatures and strain rates are investigated. The influences of single vacancy (SV), Stone-Waals (SW), and clustered vacancy (CV) defects on these properties are also studied. The findings are compared against those reported for graphene and hexagonal boron nitride (hBN). The results show that the strength of C3N decreases with increasing temperature and/or decreasing the strain rate. They also indicate that CV defects deteriorate the mechanical properties of C3N to a greater degree than SV and SW defects. At the same defect concentration, C3N shows a lower sensitivity in its stress and strain at failure to the defects compared with graphene and hBN. For example, 3% SV can reduce the failure stress of graphene and hBN by 75% and 73%, respectively, while this reduction is 54% for C3N. For the failure strain, these reductions are 72%, 63%, and 48% for graphene, hBN, and C3N, respectively.