Catalytic Deactivation and Regeneration of Nickel Microparticles in a Home-Built Microchannel-Coupled Millireactor: Substrate Specificity and Multiphase Flow Dependency.

Substrate-assisted product desorption often proposed in heterogeneous catalysis (nanozymes) denounces the catalytic deactivation of these catalysts. On the contrary, the catalytic deactivation of rigid heterogeneous catalyst becomes noticeable in a continuous flow reactor. Surprisingly, it has been addressed inadequately and in an isolated manner. In this study, we have developed a cost-effective non-lithographic method for the fabrication of a PDMS-based microchannel-coupled-millreactor. Immobilized nickel particles are resistant to leaching in the flow process. During continuous operation, millireactors show a strong catalytic activity for reduction of resazurin and p-nitrophenol with a conversion rate of almost 100 %. Catalytic poisoning is ubiquitous and gets gradually prominent whereas complete catalytic deactivation of magnetic Ni-microparticles is found to be an instantaneous process. Relatively large-sized resorufin binds predominantly to the surface and thereby blocks the access of the substrate to the Ni-particles. The dissociations of product molecules - resorufin and p-aminophenol are the rate-limiting steps that caused the abrupt deactivation of Ni-microparticle. The kinetic mechanism of heterogeneous derived from the Langmuir-Hinshelwood mechanism satisfactorily explains the catalytic poisoning and deactivation of nickel microparticles. This study sheds light on the intricacies of catalytic activity and poisoning of magnetic nickel microparticles.

Bruchid beetle ovipositioning mediated defense responses in black gram pods.

BACKGROUND: Black gram [Vigna mungo (L)] seeds are a rich source of digestible protein and dietary fibre, both for human and animal consumption. However, the quality and quantity of the Vigna seeds are severely affected by bruchid beetles during storage. Therefore, analyses of the expression of the bruchid induced transcript dynamics in black gram pods would be helpful to understand the underlying defense mechanism against bruchid oviposition. RESULTS: We used the RNAseq approach to survey the changes in transcript profile in the developing seeds of a moderately resistant cultivar IC-8219 against bruchid oviposition using a susceptible cultivar T-9 as a control. A total of 96,084,600 and 99,532,488 clean reads were generated from eight (4 each) samples of IC-8219 and T-9 cultivar, respectively. Based on the BLASTX search against the NR database, 32,584 CDSs were generated of which 31,817 CDSs were significantly similar to Vigna radiata, a close relative of Vigna mungo. The IC-8219 cultivar had 630 significantly differentially expressed genes (DEGs) of which 304 and 326 genes up and down-regulated, respectively. However, in the T-9 cultivar, only 168 DEGs were identified of which 142 and 26 genes up and down-regulated, respectively. The expression analyses of 10 DEGs by qPCR confirmed the accuracy of the RNA-Seq data. Gene Ontology and KEGG pathway analyses helped us to better understand the role of these DEGs in oviposition mediated defense response of black gram. In both the cultivars, the most significant transcriptomic changes in response to the oviposition were related to the induction of defense response genes, transcription factors, secondary metabolites, enzyme inhibitors, and signal transduction pathways. It appears that the bruchid ovipositioning mediated defense response in black gram is induced by SA signaling pathways and defense genes such as defensin, genes for secondary metabolites, and enzyme inhibitors could be potential candidates for resistance to bruchids. CONCLUSION: We generated a transcript profile of immature black gram pods upon bruchid ovipositioning by de novo assembly and studied the underlying defense mechanism of a moderately resistant cultivar.

Evolution of Micron-Spaced Patterns within Precipitating Patterns of In Situ Synthesized Silver Nanoparticles in a Nanodot-Embedded PVA/PVP Film.

Periodic pattern formation beyond conventional precipitation reactions of electrolytes is of greater importance for gaining insights into the driving forces behind spontaneous spatiotemporal pattern formation in living matter. The Liesegang phenomenon is considered to be one of the important models for understanding well-defined periodic patterns. In this study, we have used biomolecule-derived photoluminescent carbon nanodots as reducing agents that were embedded in thin polymer films. The poor water content of polyvinyl alcohol/polyvinyl pyrrolidone films has been found to dictate the temporal scale of reaction-diffusion kinetics. Moreover, the precursors for the synthesis of nanodots have been varied to decipher the role of thiol groups present in glutathione in micron-spaced pattern formation of silver nanoparticles. A method to develop periodic patterns of plasmonic silver nanoparticles is of significant interest from technological aspects. Moreover, the formation of a micron-spaced pattern has been rationed by invoking a lowered nucleation threshold in terms of slow reaction-controlled aggregation. We expect that such an understanding of the chemical reaction-based pattern formation will help in resolving the formation of artistic spatiotemporal patterns in nature.

Mitochondria-Targeting Click-Derived Pyridinyltriazolylmethylquinoxaline-Based Y-Shaped Binuclear Luminescent Ruthenium(II) and Iridium(III) Complexes as Cancer Theranostic Agents.

Due to several negative issues, market available drugs have been gradually losing their importance in the treatment of cancer. With a view to discover suitable drugs capable of diagnosing as well as inhibiting the growth of cancer cells, we have aspired to develop a group of theranostic metal complexes which will be (i) target specific, (ii) cytoselective, thus rendering the normal cell unaffected, (iii) water-soluble, (iv) cancer cell permeable, and (v) luminescent, being beneficial for healing the cancer eternally. Therefore, to reach our goal, we have prepared novel Ru(II)- and Ir(III)-based bimetallic and hetero bimetallic scaffolds using click-derived pyridinyltriazolylmethylquinoxaline ligands followed by metal coordination. Most of the compounds have displayed significant cytoselectivity against colorectal adenocarcinoma (Caco-2) and epithiloid cervical carcinoma (HeLa) cells with respect to normal human embryonic kidney cells (HEK-293) compared to cisplatin [cis-diamminedichloroplatinum(II)] along with excellent binding efficacy with DNA as well as serum albumin. Complex [(η6-p-cymene)(η5-Cp*)RuIIIrIIICl2(K2-N,N-L)](PF6)2 [RuIrL] exhibited the best cytoselectivity against all the human cancer cells and was identified as the most significant cancer theranostic agent in terms of potency, selectivity, and fluorescence quantum yield. Investigation of the localization of complex [Ir2L] and [RuIrL] in the more aggressive colorectal adenocarcinoma cell HT-29 indicates that mitochondria are the key cellular target for destroying cancer cells. Mitochondrial dysfunction and G2/M phase cell cycle arrest in HT-29 cell were found to be involved in the apoptotic cell death pathway induced by the test complexes [Ir2L] and [RuIrL]. These results validate the concept that these types of complexes will be reasonably able to exert great potential for tumor diagnosis as well as therapy in the near future.

Insights into the mode of flavin mononucleotide binding and catalytic mechanism of bacterial chromate reductases: A molecular dynamics simulation study.

Enzymes from natural sources protect the environment via complex biological mechanisms, which aid in reductive immobilization of toxic metals including chromium. Nevertheless, progress was being made in elucidating high-resolution crystal structures of reductases and their binding with flavin mononucleotide (FMN) to understand the underlying mechanism of chromate reduction. Therefore, herein, we employed molecular dynamics (MD) simulations, principal component analysis (PCA), and binding free energy calculations to understand the dynamics behavior of these enzymes with FMN. Six representative chromate reductases in monomeric and dimeric forms were selected to study the mode, dynamics, and energetic component that drive the FMN binding process. As evidenced by MD simulation, FMN prefers to bind the cervix formed between the catalytic domain surrounded by strong conserved hydrogen bonding, electrostatic, and hydrophobic contacts. The slight movement and reorientation of FMN resulted in breakage of some crucial H-bonds and other nonbonded contacts, which were well compensated with newly formed H-bonds, electrostatic, and hydrophobic interactions. The critical residues aiding in tight anchoring of FMN within dimer were found to be strongly conserved in the bacterial system. The molecular mechanics combined with the Poisson-Boltzmann surface area binding free energy of the monomer portrayed that the van der Waals and electrostatic energy contribute significantly to the total free energy, where, the polar solvation energy opposes the binding of FMN. The proposed proximity relationships between enzyme and FMN binding site presented in this study will open up better avenues to engineer enzymes with optimized chromate reductase activity for sustainable bioremediation of heavy metals.

Improving linearity by introducing Al in HfO2 as a memristor synapse device.

Artificial synapse having good linearity is crucial to achieve an efficient learning process in neuromorphic computing. It is found that the synaptic linearity can be enhanced by engineering the doping region across the switching layer. The nonlinearity of potentiation and depression of the pure device is 36% and 91%, respectively; meanwhile, the nonlinearity after doping can be suppressed to be 22% (potentiation) and 60% (depression). Henceforth, the learning accuracy of the doped device is 91% with only 13 iterations; meanwhile, the pure device is 78%. A detailed conduction mechanism to understand this phenomenon is proposed.

Transcript profiling of chickpea pod wall revealed the expression of floral homeotic gene AGAMOUS-like X2 (CaAGLX2).

The differentially expressed genes in the chickpea pod wall have been identified for the first time using a forward suppression subtractive hybridization (SSH) library. In all, 226 clones of SSH library were sequenced and analyzed. A total of 179 high-quality expressed sequence tags (ESTs) were generated and based on the CAP3 assembly of these ESTs, 126 genes (97 singletons and 29 contigs) were computationally annotated. The mapping of 88.26% ESTs by gene ontology (GO) annotation distributed them into 751 GO terms of three categories, cellular location, molecular function, and biological process. The KEGG pathway analysis revealed 45 ESTs are involved in 49 different biological pathways. Also, 67 ESTs encodes four different classes of enzymes such as oxidoreductases (29), transferase (20), hydrolases (16) and isomerase (2). Six genes were selected and subjected to qPCR analysis, of these, two genes (FHG Floral homeotic AGAMOUS-like isoform X2, MADS1 MADS-box transcription factor) showed significant up-regulation in the pod wall compared to leaves. Surprisingly, one of the MADS1 box gene, FHG (CaAGLX2), responsible for flower development expressed in the pod wall. Therefore, understanding its specific role in the pod wall could be interesting. Thus, the transcript dynamics of the chickpea pod wall revealed differentially expressed genes in the pod wall, which may be participating in the metabolic build-up of both pod wall and seeds.

Direct substitution and assisted dissociation pathways for turning off transcription by a MerR-family metalloregulator.

Metalloregulators regulate transcription in response to metal ions. Many studies have provided insights into how transcription is activated upon metal binding by MerR-family metalloregulators. In contrast, how transcription is turned off after activation is unclear. Turning off transcription promptly is important, however, as the cells would not want to continue expressing metal resistance genes and thus waste energy after metal stress is relieved. Using single-molecule FRET measurements we studied the dynamic interactions of the copper efflux regulator (CueR), a Cu(+)-responsive MerR-family metalloregulator, with DNA. Besides quantifying its DNA binding and unbinding kinetics, we discovered that CueR spontaneously flips its binding orientation at the recognition site. CueR also has two different binding modes, corresponding to interactions with specific and nonspecific DNA sequences, which would facilitate recognition localization. Most strikingly, a CueR molecule coming from solution can directly substitute for a DNA-bound CueR or assist the dissociation of the incumbent CueR, both of which are unique examples for any DNA-binding protein. The kinetics of the direct protein substitution and assisted dissociation reactions indicate that these two unique processes can provide efficient pathways to replace a DNA-bound holo-CueR with apo-CueR, thus turning off transcription promptly and facilely.

Exploring the structural assembly of rice ADP-glucose pyrophosphorylase subunits using MD simulation.

ADP-glucose pyrophosphorylase plays a pivotal role as an allosteric enzyme, essential for starch biosynthesis in plants. The higher plant AGPase comparises of a pair of large and a pair of small subunits to form a heterotetrameric complex. Growing evidence indicates that each subunit plays a distinct role in regulating the underlying mechanism of starch biosynthesis. In the rice genome, there are four large subunit genes (OsL1-L4) and three small subunit genes (OsS1, OsS2a, and OsS2b). While the structural assembly of cytosolic rice AGPase subunits (OsL2:OsS2b) has been elucidated, there is currently no such documented research available for plastidial rice AGPases (OsL1:OsS1). In this study, we employed protein modeling and MD simulation approaches to gain insights into the structural association of plastidial rice AGPase subunits. Our results demonstrate that the heterotetrameric association of OsL1:OsS1 is very similar to that of cytosolic OsL2:OsS2b and potato AGPase heterotetramer (StLS:StSS). Moreover, the yeast-two-hybrid results on OsL1:OsS1, which resemble StLS:StSS, suggest a differential protein assembly for OsL2:OsS2b. Thus, the regulatory and catalytic mechanisms for plastidial AGPases (OsL1:OsS1) could be different in rice culm and developing endosperm compared to those of OsL2:OsS2b, which are predominantly found in rice endosperm.

All oxide based flexible multi-folded invisible synapse as vision photo-receptor.

All oxide-based transparent flexible memristor is prioritized for the potential application in artificially simulated biological optoelectronic synaptic devices. SnOx memristor with HfOx layer is found to enable a significant effect on synaptic properties. The memristor exhibits good reliability with long retention, 104 s, and high endurance, 104 cycles. The optimized 6 nm thick HfOx layer in SnOx-based memristor possesses the excellent synaptic properties of stable 350 epochs training, multi-level conductance (MLC) behaviour, and the nonlinearity of 1.53 and 1.46 for long-term potentiation and depression, respectively, and faster image recognition accuracy of 100% after 23 iterations. The maximum weight changes of -73.12 and 79.91% for the potentiation and depression of the synaptic device, respectively, are observed from the spike-timing-dependent plasticity (STDP) characteristics making it suitable for biological applications. The flexibility of the device on the PEN substrate is confirmed by the acceptable change of nonlinearities up to 4 mm bending. Such a synaptic device is expected to be used as a vision photo-receptor.

Validation of novel catechol derivatives as potent Escherichia coli MetAP inhibitors using Molecular Docking and Molecular Dynamics Simulation.

BACKGROUND: Urinary tract infections (UTIs) are the most common form of nosocomial infection primarily caused by Escherichia coli. Complicated UTIs carry a higher risk of treatment failure, recurrent infections, and increased morbidity. Methionine aminopeptidase (MetAP) has gained tremendous importance as a bacterial drug target due to its role in cell growth and membrane integrity. However, the participation of metal-chelating residues and the occurrence of the enzyme in the human body complicate the process of selecting a suitable inhibitor. AIMS: This study aimed to find new molecules with more stable binding against urinary tract infection drug targets. OBJECTIVE: The objective of this study was to find new molecules with more stable binding against urinary tract infection drug targets using computational approaches. METHOD: The drug target was selected based on a literature study. Catechol derivatives were prepared and an ADME/T study was performed, followed by molecular docking and molecular dynamics. RESULT: The docking score of Met592 (-20.95) was found to be much better than that of known inhibitors (-12.88). The overall study on Rg signified that the ligand binding compels the respective proteins to become more compact and less flexible in the case of Met592. Binding free energy analysis also showed a better affinity for Met592 (-46.60) than the known inhibitor (-31.37). CONCLUSION: The increased binding score, good oral bioavailability, and better binding free energy endorse the reliability of the ligand Met592, i.e., (R, E)-4-(4-(2-(((9H-purin-6-yl)amino)methyl)- 4,5-dimethylphenyl)thiazol-2-yl)-4-aminobut-2-enoic acid, as the probable drug candidate to treat uropathogenic E. coli.

Luminescent 11-{Naphthalen-1-yl}dipyrido[3,2-a:2',3'-c]phenazine-Based Ru(II)/Ir(III)/Re(I) Complexes for HCT-116 Colorectal Cancer Stem Cell Therapy.

Due to a number of unpleasant considerations, marketed drugs have steadily lost their importance in the treatment of cancer. In order to find a viable cancer cell diagnostic agent, we therefore focused on metal complexes that displayed target adequacy, permeability to cancer cells, high standard water solubility, cytoselectivity, and luminescent behavior. In this aspect, luminescent 11-{naphthalen-1-yl} dipyrido [3,2-a:2',3'-c] phenazine based Ru(II)/Ir(III)/Re(I) complexes have been prepared for HCT-116 colorectal cancer stem cell therapy. Our study successfully established the possible cytotoxicity of IrL complex at different doses on HCT-116 colorectal cancer stem cells (CRCSCs). Additionally, an immunochemistry analysis of the complex IrL showed that the molecule was subcellularly localized in the nucleus and other regions of the cytoplasm, where it caused nuclear DNA damage and mitochondrial dysfunction. The level of BAX and Bcl-2 was further quantified by qRT-PCR. The expression of proapoptotic BAX showed increased expression in the complex IrL-treated cell compared to the control, indicating the potential of complex IrL for apoptotic induction. Upon further validation, complex IrL was developed as an inhibitor of autophagy for the eradication of cancer stem cells.

6-Shogaol Exhibits Anti-viral and Anti-inflammatory Activity in COVID-19-Associated Inflammation by Regulating NLRP3 Inflammasomes.

Recent global health concern motivated the exploration of natural medicinal plant resources as an alternative target for treating COVID-19 infection and associated inflammation. In the current study, a phytochemical, 6-shogaol [1-(4-hydroxy-3-methoxyphenyl)dec-4-en-3-one; 6-SHO] was investigated as a potential anti-inflammatory and anti-COVID-19 agent. In virus release assay, 6-SHO efficiently (94.5%) inhibited SARS-CoV2 replication. When tested in the inflammasome activation model, 6-SHO displayed mechanistic action by regulating the expression of the inflammasome pathway molecules. In comparison to the existing drugs, remdesivir and hydroxy-chloroquine, 6-SHO was not only found to be as effective as the standard anti-viral drugs but also much superior and safe in terms of predicted physicochemical properties and clinical toxicity. Comparative molecular dynamics simulation demonstrated a stable interaction of 6-SHO with NLRP3 (the key inflammasome regulator) in the explicit water environment. Overall, this study provides important cues for further development of 6-SHO as potential anti-inflammatory and anti-viral therapeutic agents.

PVDF-directed synthesis, stability and anion exchange of cesium lead bromide nanocrystals.

Photoluminescent perovskite nanocrystals are mostly used along with base materials such as polymers for material processing and large-scale production purpose. However, the role of polymer in crystal structure engineering and thereby dictating the emission properties of lead halide perovskite nanocrystals has been poorly understood. First, we have developed a polymer-directed antisolvent method for synthesis of halide perovskite crystals at room temperature and observed that the thermodynamic stabilities of crystals drive the formation of perovskite composite crystal of orthorhombic Cs4PbBr6and monoclinic CsPbBr3. Surprisingly, hydrophobic polyvinylidene fluoride (PVDF) can reduce the size of perovskite crystals to nano dimensions even at room temperature. On the other hand, perovskite nanocrystals, CsPbBr3synthesized by modified hot-injection method undergo rapid encapsulation in PVDF matrices. The size of the encapsulated nanocrystal in PVDF matrices ranges in 88 ± 32 nm. We have illustrated that there are three types of radiative recombination predominantly operative in nanocrystals-doped polymer- (i) surface defect caused radiative recombination (0.6-3 ns), (ii) exciton recombination (3-15 ns), and (iii) shallow trap assisted recombination (10-50 ns). The interface created at nanocrystal and polymer plays a decisive role in populating the shallow trap states in perovskite-polymer nanocomposite. These nanocomposites undergo fast halide exchange in aqueous hydroiodic acid solution and possess remarkable enhancement of water-/photo-stability. This research would pave way for their greater use in hydrogen production and light-emitting devices.

Ion accumulation-induced capacitance elevation in a microporous graphene-based supercapacitor.

High-performance porous 3D graphene-based supercapacitors are one of the most promising and challenging directions for future energy technologies. Microporous graphene has been synthesized by the pyrolysis method. The fabricated lightweight graphene with a few layers (FLG) has an ultra-high surface area of 2266 m2 g-1 along with various-sized micropores. The defect-induced morphology and pore size distribution of the fabricated graphene are examined, and the results show that the micropores vary from 0.85 to 1.9 nm and the 1.02 nm pores contribute 30% of the total surface area. The electrochemical behaviour of the electrode fabricated using this graphene has been studied with various concentrations of the KOH electrolyte. The highest specific capacitance of the graphene electrode of 540 F g-1 (close to the theoretical value, ∼550 F g-1) can be achieved by using the 1 M KOH electrolyte. This high specific capacitance contribution involves the counter ion adsorption, co-ion desorption, and ion permutation mechanisms. The formation of a Helmholtz layer, as well as the diffusion of the electrolyte ions, confirms this phenomenon. The symmetrical solid-state supercapacitor fabricated with the graphene electrodes and PVA-KOH gel as the electrolyte exhibits excellent energy and power densities of 18 W h kg-1 and 10.2 kW kg-1, respectively. This supercapacitor also shows a superior 100% coulombic efficiency after 6000 cycles.

Iridium(III)-Cp*-(imidazo[4,5-f][1,10]phenanthrolin-2-yl)phenol analogues as hypoxia active, GSH-resistant cancer cytoselective and mitochondria-targeting cancer stem cell therapeutic agents.

Herein, we have introduced a series of iridium(III)-Cp*-(imidazo[4,5-f][1,10]phenanthrolin-2-yl)phenol complexes via a convenient synthetic methodology, which act as hypoxia active and glutathione-resistant anticancer metallotherapeutics. The [IrIII(Cp*)(L5)(Cl)](PF6) (IrL5) complex exhibited the best cytoselectivity, GSH resistance and hypoxia effectivity in HeLa and Caco-2 cells among the synthesized complexes. IrL5 also exhibited highly cytotoxic effects on the HCT-116 CSC cell line. This complex was localized in the mitochondria and subsequent mitochondrial dysfunction was observed via MMP alteration and ROS generation on colorectal cancer stem cells. Cell cycle analysis also established the potential of this complex in mediating G2/M phase cell cycle arrest.

Modelling and Evolution of Conducting Filament in TiOx Memristor Using Conducting Atomic Force Microscopy.

Conducting filament evolution in TiOx based resistive switching memory fabricated by simple oxidation of Ti film is investigated. Formation of titanium oxide is confirmed from the X-ray diffraction study. Forming is required to initiate the switching process. A bipolar analog switching is observed with a positive set and negative reset voltage. The switching properties in TiOx layer owing to the formation of conducting filament is confirmed from the conducting atomic force micrograph at different bias voltage. A significant change in surface topography as a filament formation during set and reset is presented. Conduction mechanism inside the device at various voltage and effect of tunnel width on current is studied. The effective tunnel width of conduction filament and related parameters for device using device modelling (Threshold Adaptive Memristor model) is studied. The device can be used for synaptic applications.

Understanding the thermal response of rice eukaryotic transcription factor eIF4A1 towards dynamic temperature stress: insights from expression profiling and molecular dynamics simulation.

Eukaryotic translation initiation factors (eIFs) are the group of regulatory proteins that are involved in the initiation of translation events. Among them, eIF4A1, a member of the DEAD-box RNA helicase family, participates in a wide spectrum of activities which include, RNA splicing, ribosome biogenesis, and RNA degradation. It is well known that ATP-binding and subsequent hydrolysis activities are crucial for the functionality of such helicases. Although the stress-responsive upregulation of eIF4A1 has been reported in plants during stress, it is difficult to anticipate the functionality of the corresponding protein product. Therefore, to understand the activity of eIF4A1 in rice in response to temperature stress, we first conducted an expression analysis of the gene and further investigated the structural stability of the eIF4A1-ATP/Mg2+ complex through molecular dynamics (MD) simulations at different temperature conditions (277 K, 300 K, and 315 K). Our results demonstrated a three to fourfold increased expression of rice eIF4A1 both in root and shoot at 42 °C compared to control. Furthermore, the MD simulation portrayed strong ATP/Mg2+ binding at a higher temperature in comparison to control and cold temperature. Overall, the increased expression pattern of eIF4A1 and strong ATP/Mg2+ binding at higher temperature indicated the heat stress-tolerant capacity of the gene in rice. The results from our study will help in understanding the activity of gene and guide the researchers for screening of novel stress inducible candidate genes for the engineering of temperature stress tolerant plants.Communicated by Ramaswamy H. Sarma.

GSH-resistant and highly cytoselective ruthenium(II)-p-cymene-(imidazo[4,5-f][1,10]phenanthrolin-2-yl)phenol complexes as potential anticancer agents.

To avoid the side effects of the current popular platinum-based anticancer drugs, researchers have made tireless attempts to design appropriate GSH-resistant Ru(ii)-arene complexes. In this regard, luminescent ruthenium(ii)-p-cymene-imidazophenanthroline complexes were developed as promising highly cytoselective cancer theraputic agents for HeLa and Caco-2 cells.

Structural Elucidation of Inter-CARD Interfaces involved in NOD2 Tandem CARD Association and RIP2 Recognition.

Nucleotide-binding and oligomerization domain-containing protein 2 (NOD2) recognizes the muramyl dipeptide and activates the NF-κB signaling cascade following its interaction with receptor-interacting protein 2 (RIP2) via caspase recruitment domains (CARDs). The NOD2-RIP2 interaction is not understood well due to inadequate structural information. Using comparative modeling and multimicrosecond timescale molecular dynamics simulations, we have demonstrated the association of NOD2-CARDs (CARDa-CARDb) and their interaction with RIP2CARD. Our results suggest that a negatively charged interface of NOD2CARDa and positively charged type-Ia interface of NOD2CARDb are crucial for CARDa-CARDb association and the type-Ia interface of NOD2CARDa and type-Ib interface of RIP2CARD predicted to be involved in 1:1 CARD-CARD interaction. Moreover, the direct interaction of NOD2CARDb with RIP2CARD signifies the importance of both CARDs of NOD2 in RIP2-mediated CARD-CARD interaction. Altogether, the structural results could help in understanding the underlying molecular details of the NOD2-RIP2 association in higher and lower eukaryotes.