Evaluating the MDCK cell permeability of greenly synthesize bimetallic Ag/Zn Nanoparticles using leaf extract of Vallaris solanacea as a potential antipesticide-resistant agent

: Bimetallic nanoparticles, particularly Ag/Zn bimetallic nanoparticles, have gained increasing attention due to their unique properties, making them suitable for a variety of applications such as catalysis, water treatment, and environmental remediation. This study aimed to elucidate the use of bimetallic nanoparticles of Ag/Zn as an alternative to resistant pesticides for pest control. Furthermore, this research demonstrates that BNPs can target speci ﬁ c pollutants and degrade them through various mechanisms. BNP docking with the Nilaparvata lugens cytochrome P450 (CYP6ER1) protein exhibited the lowest binding energy of − 7.5 kcal/mol. The cell permeability analysis of BNP in plant cells reveals that the BNP has 0 % permeability towards any cell at − 10 kcal/mol energy, which is the lowest free energy translocation pathway. The harmful leftover residues of the pesticides have a higher chance of degradability in case of interaction with BNP validated by chemical – chemical interaction analysis. Additionally, MDCK permeability coe ﬃ cient of small molecules based on the regression model was calculated for BNP which authenticated the e ﬃ ciency of BNP. Moreover, Swiss ADMET simulated absorption using a boiled egg model with no blood – brain barrier and gastrointestinal crossing for the expected BNP molecule has been observed. Signi ﬁ cantly, the ﬁ ndings indicate that employing bimetallic nanoparticles like Ag/Zn is a crucial strategy for bioremediation because they pro ﬁ ciently decompose pesticides while posing no risk to humans. Our results will facilitate the design of novel BNPs materials for environmental remediation and pest control ensuring human health safety that are predicated on bimetallic nanoparticles.


Introduction
Pesticides are any chemical or biological material that is commonly used in agriculture to protect crops from pests and diseases, which can help to enhance crop yields and improve food security.Pesticides can be broken down into two categories: chemical pesticides and biological pesticides.The use of pesticides in large-scale agriculture decreases the amount of work required, allowing for greater productivity [1].As an additional benefit, it helps keep food safe by decreasing spoilage and preventing disease during storage.They have the potential to boost agricultural productivity, providing more financial benefits to farmers and the agricultural industry as a whole [2].A wide variety of health issues, including cancer, birth deformities, and neurological damage can result from its improper usage and management, and it can have detrimental consequences on both human health and the environment.The breakdown of pesticides in the environment is a slow and complicated process, and over time, pests have developed resistance against them.This resistance occurs when an insect population becomes less responsive to a specific pesticide, rendering its proper usage ineffective [3].Using the same pesticide or one with a similar mechanism of action repeatedly can lead to the development of resistance, which is a major problem that is progressively worsening.
Currently, over 600 insect species have evolved resistance to one or more types of pesticides.When pests become resistant to a particular pesticide or group of pesticides, fewer control options are available to manage these pests [4].
People frequently depend heavily on pesticides as their primary method for controlling pests.This creates a greater likelihood for the development of resistance, as pesticides that do not degrade quickly continue to contribute to selection for resistant strains, even after they are no longer being used.Pests with limited areas to inhabit are at a higher risk of developing resistance since they are subjected to higher concentrations of pesticides and have fewer chances to mate with populations that have no't been exposed [5].These pests develop resistance by undergoing physiological changes that provide protection against the chemicals.There are two types of resistance including multiple and cross resistance.Pests that are resistant to multiple classes of pesticides are known as "multiple-resistance pests."This can occur when pesticides are used in a sequence, where a new class of pesticide replaces one that the pests have already developed resistance to.Another related phenomenon called "cross-resistance" happens when the genetic mutation that gave the pests resistance to one pesticide also makes them resistant to others that work in a similar way [6].
Proteinase inhibitors, phytolectin, amylase inhibitors, and chitinase are genes that come from plants and are part of their natural defense mechanisms against insect attacks.On the other hand, animal sources of genes that provide resistance against insects include wasps, spiders, scorpions, and mammals.Various pesticides such as 2,4-dichlorophenoxyacetic acid (2,4-D), aldrin/dieldrin, atrazine, chlordane, chlordecone, endosulfan, glyphosate, hexachlorobenzene, methoxychlor, pentachlorophenol, and toxaphene have been utilized to combat pests, but a significant number of them have lost their effectiveness due to pest resistance [7].The use of pesticides is on the rise worldwide, with developing countries having the highest consumption.However, pesticides can have harmful effects on non-target species such as pollinators, beneficial insects, birds, and other wildlife.Biological control, which employs natural predators, parasites, and pathogens to manage pests, is an alternative approach.The conventional methods for detecting and breaking down pesticides are frequently insufficient, and more effective solutions are necessary [8].
Nanoparticles present a promising alternative solution due to their capability to target specific pollutants and break them down using various mechanisms.With regards to pesticide detection, nanoparticles can be designed to attach themselves to particular pesticides, which enable the development of sensors that are both sensitive and selective [9].Additionally, nanoparticles can be utilized to enhance the breakdown of pesticides in the environment through advanced oxidation procedures.Bimetallic nanoparticles, particularly Ag/Zn bimetallic nanoparticles, have become increasingly popular due to their unique properties that make them suitable for various applications such as catalysis, water treatment, and environmental remediation [10][11][12][13][14].Despite their potential benefits, the conventional methods for synthesizing bimetallic nanoparticles often involve the use of hazardous and environmentally harmful substances, posing challenges for their large-scale production and widespread utilization [10][11][12][13][14]. Considering these limitations, our study seeks to explore an innovative approach by employing plant extracts in the synthesis process.This green synthesis not only mitigates the environmental impact but also enhances the overall applicability of Ag/Zn bimetallic nanoparticles.By doing so, we aim to contribute to the development of eco-friendly and scalable methods for producing nanoparticles, ensuring their efficacy in addressing environmental challenges, particularly in the context of pesticide degradation.
In this method, bimetallic nanoparticles serve a dual role as both reducing and stabilizing agents, with the unique approach of utilizing plant extracts.This not only reduces the toxicity and cost associated with synthesis but also yields distinctive and highly efficient nanoparticles.The synthesis of Ag/Zn bimetallic nanoparticles will undergo scrutiny through a combination of laboratory experiments and computational simulations.These investigations will encompass various chemical interactions to convincingly demonstrate that bimetallic nanoparticles emerge as exceptionally effective agents against pests.The primary objective of our study is to showcase the potential of green synthesis in producing bimetallic nanoparticles characterized by high activity and stability.These nanoparticles will not only target pests but also play a crucial role in degrading pesticides.Importantly, this degradation process is designed to be environmentally friendly, ensuring that it does not harm plants or crops.The outcomes of this research endeavor aim to contribute significantly to the development of new and innovative materials based on bimetallic nanoparticles.These materials have the potential to serve as effective tools for environmental remediation, safeguarding both human health and the environment from the adverse impacts of pesticides.

Preparation of V. Solanacea plant extract
Fresh leaves were rinsed thoroughly with water three times to remove any dirt or debris.Subsequently, the leaves were sliced into small fragments and subjected to shadow drying for 14-15 days in a well-ventilated area or an oven at a room temperature of 25-30 °C until completely dry [15].The dried leaves were then ground into a fine powder using a blender.To prepare the extract, 15 g of the powdered leaves were added to a 1,000 mL Erlenmeyer flask, which was covered with 500 mL of distilled water.The flask was placed on a hot plate magnetic stirrer for 3-4 h at a temperature of 60 °C and a stirring speed of 1,500 rpm.After completion of the extraction, the extract was filtered through filter paper to remove any solid particles and stored in a clean, glass container with a lid in a refrigerator at 4 °C or in a cool, dark place until further use.

Biosynthesis of Ag/Zn bimetallic nanoparticles
A preparation was made by combining 10 mL of plant extract with 10 mL of a 0.50 mM AgNO 3 working solution, and the mixture was stirred using a magnetic stirrer at room temperature for 30 min.Following this, 10 mL of a 0.25 mM zinc nitrate (Zn(NO 3 ) 2 ) solution was added, and the stirring continued for an additional 30 min [16].To achieve a pH of 9, the mixture's pH was adjusted using 0.1 M NaOH.Subsequently, the mixture was heated on a heating mantle at 60 °C for 4 h while maintaining constant stirring and then allowed to cool down to room temperature.The resulting mixture was then centrifuged at 10,000 rpm for 30 min to collect the pellet containing the bimetallic nanoparticles.Several rinses with distilled water and methanol were performed to eliminate excess plant extract and other impurities from the collected nanoparticles.

UV-visible spectrophotometer
The presence of bimetallic nanoparticles was verified through spectrophotometric analysis.The band between 200 and 800 nm was examined using surface plasmon resonance (SPR) analysis.This band, which was activated by the surface plasmon vibration and is linked to the absorption of bimetallic nanoparticles in the range of 250-550 nm, further demonstrates their presence.

FTIR spectroscopy
FTIR (Fourier-transform infrared) spectroscopy was employed in this study to analyze the functional groups involved in the synthesis of bimetallic nanoparticles.FTIR is a well-established technique used for the identification and characterization of various functional groups [17].To facilitate the measurements, the nanoparticle solution was subjected to centrifugation at 1,000 rpm for 30 min.This centrifugation step aimed to separate any remaining impurities or unwanted particles, ensuring the accuracy and reliability of the FTIR analysis.Following centrifugation, the resulting supernatant was carefully removed, and the sample was then prepared for FTIR measurement.

SEM (scanning electron microscope) analysis
The structure of the synthesized nanoparticles was examined through scanning electron microscopy (SEM) analysis.On double conductive tape, synthesized nanoparticles were placed after drying at room temperature.To improve the conductivity of the synthesized nanoparticles, the samples were covered in a platinum-gold coating.The samples were then observed at voltages of 12.50 kV.

Energy-dispersive X-ray spectroscopy (EDX)
EDX was used to examine bimetallic nanoparticles and determine the elements on their surface.Some X-rays are bombarded onto the sample for this reason.The elemental composition of the collected diffracted rays is measured, and the results are shown on the screen.

Protein retrieval
The online database Molecular Database on Indian Insects (MODII) contains a number of databases, including Insect Pest Info, Insect Barcode Information System (IBIn), Insect Whole Genome sequencing (WGS), Other Genomic Resources (OGR) of National Bureau of Agricultural Insect Resources (NBAIR), Whole Genome Sequencing of Honeybee Viruses (hBV), Genomic tools (iGenTools), and Insecticide Resistance Gene Database (IRGD) (https://cib.res.in/irgd/index.php)[18].This database was created using a comprehensive strategy and offers data on the phenotypic and genetic characteristics of integral insects significant in agriculture.The protein CYP6ER1's amino acid sequence was retrieved from the insect resistance gene database.

Secondary structure evaluation
An eminent web service offering a wide range of protein prediction and annotation tools with a primary focus on protein structural annotations is the PSIPRED Protein Analysis Workbench (http://bioinf.cs.ucl.ac.uk/psipred/).PsiPred was assessed for the prediction of the secondary structure of the protein Nilaparvata lugens cytochrome P450 (CYP6ER1).

3D structure prediction
The SWISS-MODEL server (https://swissmodel.expasy.org/) is an entirely automated work process server that streamlines the homology design modelling and facilitates the ability for users to generate precise protein models and have easy accessibility to modelling results, their visualization, and their interpretation [19].It is a pioneer in the field of automated modelling and has been consistently upgraded for the last 25 years.Swiss model created a 3D model of the protein of interest utilizing amino acid sequence of the protein CYP6ER1 as input.The protein was downloaded in pdb format, and Pymol was accessed to visualize it.

BNP structure designing
Since 1985, ChemDraw (https://perkinelmerinformatics.com/ products/research/chemdraw) a desktop program has served as the industry standard for chemical modelling.Bonds can be drawn one by one, or structures can be created using pre-made rings or templates.There are templates for several bicyclic compounds as well as for typical stereochemical diagrams like Newman projections, sawhorse structures, Fischer projections, and typical illustrations of 5-and 6-membered rings [20].The structure of BNP was chemically sketched by a combination of zinc and silver molecules to create a cohesive unified bimetallic nanoparticle structure.

Docking interaction
Autodock Vina performed the docking analysis of the protein CYP6ER1 and BNP molecule.A group of automated docking tools are included here.It is incorporated to predict how tiny compounds would interact with proteins.After the protein and ligand were prepared, the active sites were found by using the Deepsite online server, and then the grid box was set by default.Docking was carried out between BNP and protein to calculate the lowest binding energy and interaction of ligand against the targeted protein.

Cell permeability estimation of BNP in plants
The PerMM web server (https://permm.phar.umich.edu/)and databases are utilized for the quantitative investigation and visualization of passive translocation of bioactive compounds across lipid membranes.To aid in the selection and optimization of predicting leads, the server can be used to forecast the permeability coefficients of compounds with various chemical scaffolds [21].More than 500 chemicals in various membrane systems had their permeability coefficients computed and experimentally determined in contrast to BNP using the accompanying PerMM database to analyze cell permeability of BNP.

Identification of pesticides
The literature review resulted in the identification of various pesticides.For the purpose of screening effectiveness of BNP, 15 active pesticides were chosen.These pesticides' 3D structures were downloaded in SDS format from PubChem (https://pubchem.ncbi.nlm.nih.gov/) and stored in PDB format and PDB (Protein Databank), respectively.

Assessment of chemical-chemical interaction
A revolutionary online system called ChemDIS Mixture (http://cwtung.kmu.edu.tw/chemdis/mixture) is developed to assess the shared target proteins, common enhanced activities, pathways, and diseases affected by many chemicals in order to make it easier to identify potential impacts of a combination of interactions.Venn diagrams have been introduced to make it simple to analyze and see the interaction targets and effects [22].In addition to the interaction effects of the 15 pesticides with BNP, overall impacts based on the combination of interacting pesticides were also evaluated.

MDCK permeability of BNP
MDCKpred web tool (http://www.mdckpred.in/)uses a regression model built using chemical properties of membrane interactions to calculate the MDCK permeability coefficient of small molecules.The small molecule is passively diffused via a biological membrane abundant in phospholipids that are in charge of the small molecule's overall intermolecular interactions [23].This tool worked swiftly to determine the MDCK permeability coefficient (nm/s) for BNP by entering a few basic descriptors.

Physiochemical parameters and safety evaluation of BNPs
The SwissADME web tool (http://www.swissadme.ch) is designed for easy submission and result analysis.It provides exclusive access to effective techniques (like iLOGP16 or the BOILED-Egg17) and state-of-the-art free web-based tools for ADME and pharmacokinetics such as pk-CSM14 and admetSAR15 [24].BNP was given as an input in SMILES format for the computation for multiple parameters and physiochemical properties to obtain intuitive results.

Green synthesis of Ag/Zn BMNPs
The result of the synthesis of Ag/Zn bimetallic nanoparticles (BMNPs) using plant extract of Vallaris solanacea showed the successful formation of nanoparticles as shown in Figure 1B.The color of the reaction mixture changed from yellow to brown, indicating the formation of BMNPs.

Characterization of Ag/Zn nanoparticles 3.2.1 UV-visible spectrophotometer
The UV-visible absorption spectrum of Ag/Zn nanoparticles synthesized using plant extract of V. solanacea showed a peak at 400 nm as shown in Figure 2A, which indicates the synthesis of nanoparticles with a size and shape that result in strong absorption in this region.The maximum absorbance at this peak was measured to be 0.75, indicating that the sample contained a relatively high concentration of nanoparticles.

FTIR spectroscopy
Figure 2B shows the FTIR spectrum of Ag/Zn nanoparticles synthesized using plant extract of V. solanacea reveal several distinct peaks in the range 4,000-500 cm −1 .The detected functional groups along with the peaks identified from the FTIR spectrum are shown in Table 1.

Scanning electron microscopy (SEM)
The SEM images as shown in Figure 3A indicate that the nanoparticles are predominantly spherical and have an average diameter of 25 nm which was calculated using image J software.Moreover, the SEM images confirm that the Ag/Zn nanoparticles exhibit a smooth surface, without any visible agglomeration or clustering.

Energy-dispersive X-ray spectroscopy (EDX)
The EDX spectrum also showed that the relative concentrations of Ag and Fe in the nanoparticles were approximately 75 and 65 %, respectively.The EDX analysis confirmed the elemental composition of the Ag/Zn nanoparticles, which was consistent with the results obtained from other characterization techniques such as XRD and SEM (Table 2).

Pesticide resistance gene acquisition
The amino acid sequence of CYP6ER1 was accessed from MODII.Alongside, the other parameters include locus number, accession number, base pair size, gene name, and more as shown in Table 3.

Secondary structure of protein
The secondary structure of protein N. lugens cytochrome P450 (CYP6ER1) was predicted by PsiPred where the pink color depicts alpha helixes, grey color depicts coils and yellow color represent the strands respectively for 506 amino acids (Figure 4).The findings additionally show that the protein CYP6ER1 typically contain nonpolar amino acids that are represented in orange, hydrophobic amino acids in green, polar amino acids in red, and aromatic plus cysteine in light blue (Figure 5).

3D structure prediction
Swiss Model was provided the amino acid sequence of the protein CYP6ER1 that was acquired from the insect resistance gene database in order to predict its 3D structure, which is visualized using Pymol as shown in Figure 6.

Structure prediction of BNP
The 3D structure of a bimetallic nanoparticle (BNP) made of zinc and silver has been designed with the help of Chemdraw and visualized using Pymol as illustrated in Figure 7.

Docking
The target protein CYP6ER1 was docked with the BNP using Autodock Vina, and the simulated BNP docking with the protein exhibited the lowest binding energy.The binding energy of the docked model is −7.5 kcal/mol.The strength of the bonding between BNP and CYP6ER1 protein is well reflected by the docking energy.

Cell permeability prediction for plants
The cell permeability analysis of BNP in plants cells is predicted which demonstrates that the free energy of binding     4.
The following G(z) curve reveals that the BNP has 0 % permeability towards any cell at −10 kcal/mol energy, which is the lowest free energy translocation pathway (Figure 8).

Retrieval of pesticides structures
In addition to their IUPAC nomenclature and 3D structures, 15 pesticides' structures were retrieved from Puchem, as shown in Table 5.

Chemical-chemical interaction through ChemDIS
The enriched GO, route, DO, and DOLite terms for each of the 15 pesticides were ascertained initially based on the interactions it has with the BNP.The overlapped and different elements were eventually tabulated and plotted as a Venn diagram for simplified interpretation.The harmful leftover residues of the pesticides have a higher chance of degradability in case of interaction with BNP as apparent in higher values showcased as in case of interaction with BNP with respective pesticides.For examining the overall impacts of a specific set of pesticides, overall effects predicated on the union of interacting pesticides were also estimated in additament to the interaction effects as shown in the Venn diagrams below (Figure 9).

MDCK permeability analysis
MDCK permeability coefficient of small molecule based on the regression model was calculated for BNP.Initially the internal datasets were built applying the formula: Then, the external dataset was built for BNP.The datasets were converted and standardized into canonical smiles.

Table :
The table shows the analysis of BNP cell permeability in plant cells including the free energy of binding (DOPC) and other calculated parameters.Values greater than 50,000 indicate its membrane permeability of insects in comparison to existing pesticides, demonstrating the maximum level of BNPs' penetration into cells of pests.Hence, proving BNPs as a valid anti-pesticidal active candidate (Table 6).

Safety evaluation for humans
As the red dot is outside the white and yellow part depicting that it cannot be absorbed into GI tract of humans and could not cross the blood-brain barrier, declaring it safe for humans.When a molecule is present in the white area of a boiled egg model, it represents gastrointestinal absorption, and when it is present in the yellow area, it shows that the molecule has accessed the blood brain barrier (Figure 10).Conclusively, simulated absorption using a boiled egg model with no blood-brain barrier and gastrointestinal crossing for the expected BNP molecule has been observed as presented in Figure 7.

Physiochemical properties evaluation
SWISS ADMET demonstrated the physiochemical properties.Molecular weight, number of heavy atoms, number of rotable bonds, number of H-bond acceptors and H-bond donors, molar refractivity, skin permeation (Log Kp), bioavailability score, synthetic accessibility, drug likeness (Ghose), and other parameters are shown in Table 7 below.

Discussion
Globally, approximately three billion tons of pesticides are utilized annually.Despite the vast quantity of pesticides applied, pests, insects, weeds, and plant pathogens still account for the destruction of approximately 40 % of all crops.The issue of food loss to pests has taken on greater significance in the present day owing to the current global population of 6.5 billion individuals [25].Additionally, the fact that nearly 60 % of the global population suffers from malnourishment further exacerbates the gravity of this situation.A new era in chemical pest control began with the introduction of synthetic chemical pesticides such as DDT, 2,4-D, BHC, dieldrin, and others [26].These chemicals were highly effective in controlling pests, easy to apply, and acted quickly.As a result, their use spread rapidly throughout the United States and the rest of the world, and they initially fulfilled their promise in controlling pests.This led to a great deal of enthusiasm for these new chemical weapons.
However, the efficacy of DDT and other pesticides against insect pests was short-lived due to the development   Sánchez-Bayo reported that inadequate management and information concerning pesticides has led to their harmful effects and accumulation in various locations beyond crops.Globally, it is estimated that approximately 26 million human pesticide poisonings occur annually, resulting in roughly 220,000 deaths per year [27].The gradual accumulation and resistance of pesticides have adverse effects on both humans and plants, contaminating soil, water, turf, and other vegetation.Pesticides can cause a variety of health issues in humans, such as stinging eyes, rashes, blisters, blindness, nausea, dizziness, diarrhea, cancers, birth defects, reproductive harm, immunotoxicity, neurological and developmental toxicity, and disruption of the endocrine system.
Georghiou suggested that despite the growing interest in alternative methods for pest control and their integration into a rational system, it is anticipated that pesticide resistance will continue to play a central role in pest control technologies in the foreseeable future [28].However, this study proposes the use of bimetallic nanoparticles of Ag/Zn as an alternative to resistant pesticides for pest control [29].These nanoparticles are environmentally friendly and pose no harmful effects on the environment or human health.
Khan and Pathak reported that nano-based techniques, such as the use of bimetallic nanoparticles as sensors, offer the potential to detect pesticides at lower concentrations and with greater accuracy than conventional methods.Moreover, BNPs play a significant role in degrading pesticide residues and are more effective in killing pests than traditional methods.Bimetallic nanoparticles, particularly Ag/Zn bimetallic nanoparticles, have gained increasing attention due to their unique properties, making them suitable for a variety of applications such as catalysis, water treatment, and environmental remediation.Furthermore, this research demonstrates that BNPs have the ability to target specific pollutants and degrade them through various mechanisms.The chemical-to-chemical interaction of nanoparticles indicates that they exhibit greater efficiency against pesticides.The ChemDIS was also added in results for chemicalchemical interaction.This research was supported by insilico computational analysis having Autodock Vina score about −7.5 Kcal/Mol.Furthermore, the MDCK permeability of the pesticides was also calculated which showed that the BNPs of Ag/Zn can safely use against pests instead of pesticides while also helping in the degradation of harmful pesticides making BNPs eligible for multiple uses.

Conclusion
Pesticides are crucial in boosting food production by safeguarding crops against pest-borne diseases, which results in higher yields and increased food output.They come in various forms such as insecticides, herbicides, fungicides, rodenticides, and disinfectants, which are used to manage insects, weeds, fungi, rats, bacteria, viruses, and other pathogens in public health and food safety applications.However, the effectiveness of pesticides has diminished due to pest genes mutation, making them less effective and persistent in the environment for extended periods, contaminating soil, water, and air, posing potential threats to both wildlife and human health.In this study, we utilized bimetallic nanoparticles, specifically Ag/Zn, which have shown the capability to degrade pesticides.This in-silico computational analyses, such as MDCK analysis, predicted that these bimetallic nanoparticles exhibit strong permeability towards pesticide cell membranes.Furthermore, our results indicate that using bimetallic nanoparticles like Ag/Zn is an essential approach to environmental remediation, as they effectively degrade pesticides and do not pose harm to human beings.data curation, Khushbakht Javed; writingoriginal draft preparation, Ayaz Ali Khan; writingreview and editing, Thamer H Albekairi; visualization, Tariq Aziz; Supervision, Muhammad Naveed; project administration, Tariq Aziz.Competing interests: The authors declare no conflict of interest.
Research funding: No funding was received.

Figure 1 :
Figure 1: (A) Results of phytochemical screening of plant extract of V. solanacea.(B) Color change of plant extract upon adding metal ion precursor indicating the formation of Ag/Zn BMNPs.

Figure 3 :
Figure 3: (A) SEM images of Ag/Zn BNPs at 120x magnified view of nanoparticles showing average diameter of Ag/Zn BMNPs is 30nm calculated with the help of image j software.(B) EDX analysis shows the highest peaks consist of metal atoms of Ag and Fe.

Figure 4 :
Figure 4: The secondary structure of protein CYP6ER1.Pink color showing helixes, yellow color showing strands and grey color showing coils, respectively.The color coding key for other structure forms are shown as well.

Figure 5 :
Figure 5: Nonpolar amino acids are illustrated in orange, hydrophobic amino acids in green, polar amino acids in red, and aromatic plus cysteine in light blue for the secondary structure of the protein CYP6ER1.

Figure 6 :
Figure 6: Pymol visualizes the protein CYP6ER1's 3D structure that was obtained using Swiss model as seen in the figure.

Figure 7 :
Figure 7: Bimetallic nanoparticle (BNP) sketched with the help of Chemdraw and visualised using Pymol as demonstrated in Figure 4.

Figure 8 :
Figure 8: The graph shows the cell permeability curve G(z) of BNP in plant cells showing no apparent permeability at −10 kcal/mol.

Figure 10 :
Figure 10: The boiled egg model for BNP showing no permeability against blood brain barrier (yolk) and gastrointestinal tract (white) as well.

Table  :
EDX analysis shows the elemental composition of Ag/Zn BMNPs by % weight and % atomic.

Table  :
The data about Nilaparvata lugens protein CTPER accessed from Insect Resistance Gene Database, MODII.

Table  :
The list of MDCK permeability coefficient of pesticides based on regression model for BNP.