Deciphering the mechanisms and interactions of the endocrine disruptor bisphenol A and its analogs with the androgen receptor.

Bisphenol A (BPA) and its various forms used as BPA alternatives in industries are recognized toxic compounds and antiandrogenic endocrine disruptors. These chemicals are widespread in the environment and frequently detected in biological samples. Concerns exist about their impact on hormones, disrupting natural biological processes in humans, together with their negative impacts on the environment and biotic life. This study aims to characterize the interaction between BPA analogs and the androgen receptor (AR) and the effect on the receptor's normal activity. To achieve this goal, molecular docking was conducted with BPA and its analogs and dihydrotestosterone (DHT) as a reference ligand. Four BPA analogs exhibited higher affinity (-10.2 to -8.7 kcal/mol) for AR compared to BPA (-8.6 kcal/mol), displaying distinct interaction patterns. Interestingly, DHT (-11.0 kcal/mol) shared a binding pattern with BPA. ADMET analysis of the top 10 compounds, followed by molecular dynamics simulations, revealed toxicity and dynamic behavior. Experimental studies demonstrated that only BPA disrupts DHT-induced AR dimerization, thereby affecting AR's function due to its binding nature. This similarity to DHT was observed during computational analysis. These findings emphasize the importance of targeted strategies to mitigate BPA toxicity, offering crucial insights for interventions in human health and environmental well-being.

Structural insight into the mechanisms and interacting features of endocrine disruptor Bisphenol A and its analogs with human estrogen-related receptor gamma.

Bisphenol A (BPA) is a very important chemical from the commercial perspective. Many useful products are made from it, so its production is increasing day by day. It is widely known that Bisphenol A (BPA) and its analogs are present in the environment and that they enter our body through various routes on a daily basis as we use things made of this chemical in our daily lives. BPA has already been reported to be an endocrine disruptor. Studies have shown that BPA binds strongly to the human estrogen-related receptor gamma (ERRγ) and is an important target of it. This study seeks to understand how it interacts with ERRγ. Molecular docking of BPA and its analogs with ERRγ was performed, and estradiol was taken as a reference. Then, physico-chemical and toxicological analysis of BPA compounds was performed. Subsequently, the dynamic behavior of ERRγ and ERRγ-BPA compound complexes was studied by molecular dynamics simulations over 500 ns, and using this simulated data, their binding energies were again calculated using the MM-PBSA method. We observed that the binding affinity of BPA and its analogs was much higher than that of estradiol, and apart from being toxic, they can be easily absorbed in our body as their physicochemical properties are similar to those of oral medicines. Therefore, this study facilitates the understanding of the structure-activity relationship of ERRγ and BPA compounds and provides information about the key amino acid residues of ERRγ that interact with BPA compounds, which can be helpful to design competitive inhibitors so that we can interrupt the interaction of BPA with ERRγ. In addition, it provides information on BPA and its analogs and will also be helpful in developing new therapeutics.

Veterinary systems biology for bridging the phenotype-genotype gap via computational modeling for disease epidemiology and animal welfare.

Veterinary systems biology is an innovative approach that integrates biological data at the molecular and cellular levels, allowing for a more extensive understanding of the interactions and functions of complex biological systems in livestock and veterinary science. It has tremendous potential to integrate multi-omics data with the support of vetinformatics resources for bridging the phenotype-genotype gap via computational modeling. To understand the dynamic behaviors of complex systems, computational models are frequently used. It facilitates a comprehensive understanding of how a host system defends itself against a pathogen attack or operates when the pathogen compromises the host's immune system. In this context, various approaches, such as systems immunology, network pharmacology, vaccinology and immunoinformatics, can be employed to effectively investigate vaccines and drugs. By utilizing this approach, we can ensure the health of livestock. This is beneficial not only for animal welfare but also for human health and environmental well-being. Therefore, the current review offers a detailed summary of systems biology advancements utilized in veterinary sciences, demonstrating the potential of the holistic approach in disease epidemiology, animal welfare and productivity.

Identification of histidine kinase inhibitors through screening of natural compounds to combat mastitis caused by Streptococcus agalactiae in dairy cattle.

BACKGROUND: Mastitis poses a major threat to dairy farms globally; it results in reduced milk production, increased treatment costs, untimely compromised genetic potential, animal deaths, and economic losses. Streptococcus agalactiae is a highly virulent bacteria that cause mastitis. The administration of antibiotics for the treatment of this infection is not advised due to concerns about the emergence of antibiotic resistance and potential adverse effects on human health. Thus, there is a critical need to identify new therapeutic approaches to combat mastitis. One promising target for the development of antibacterial therapies is the transmembrane histidine kinase of bacteria, which plays a key role in signal transduction pathways, secretion systems, virulence, and antibiotic resistance. RESULTS: In this study, we aimed to identify novel natural compounds that can inhibit transmembrane histidine kinase. To achieve this goal, we conducted a virtual screening of 224,205 natural compounds, selecting the top ten based on their lowest binding energy and favorable protein-ligand interactions. Furthermore, molecular docking of eight selected antibiotics and five histidine kinase inhibitors with transmembrane histidine kinase was performed to evaluate the binding energy with respect to top-screened natural compounds. We also analyzed the ADMET properties of these compounds to assess their drug-likeness. The top two compounds (ZINC000085569031 and ZINC000257435291) and top-screened antibiotics (Tetracycline) that demonstrated a strong binding affinity were subjected to molecular dynamics simulations (100 ns), free energy landscape, and binding free energy calculations using the MM-PBSA method. CONCLUSION: Our results suggest that the selected natural compounds have the potential to serve as effective inhibitors of transmembrane histidine kinase and can be utilized for the development of novel antibacterial veterinary medicine for mastitis after further validation through clinical studies.

Targeting the PEDV 3CL protease for identification of small molecule inhibitors: an insight from virtual screening, ADMET prediction, molecular dynamics, free energy landscape, and binding energy calculations.

BACKGROUND: The porcine epidemic diarrhea virus (PEDV) represents a major health issue for piglets worldwide and does significant damage to the pork industry. Thus, new therapeutic approaches are urgently needed to manage PEDV infections. Due to the current lack of a reliable remedy, this present study aims to identify novel compounds that inhibit the 3CL protease of the virus involved in replication and pathogenesis. RESULTS: To identify potent antiviral compounds against the 3CL protease, a virtual screening of natural compounds (n = 97,999) was conducted. The top 10 compounds were selected based on the lowest binding energy and the protein-ligand interaction analyzed. Further, the top five compounds that demonstrated a strong binding affinity were subjected to drug-likeness analysis using the ADMET prediction, which was followed by molecular dynamics simulations (500 ns), free energy landscape, and binding free energy calculations using the MM-PBSA method. Based on these parameters, four putative lead (ZINC38167083, ZINC09517223, ZINC04339983, and ZINC09517238) compounds were identified that represent potentially effective inhibitors of the 3CL protease. CONCLUSION: Therefore, these can be utilized for the development of novel antiviral drugs against PEDV. However, this requires further validation through in vitro and in vivo studies.

Vetinformatics from functional genomics to drug discovery: Insights into decoding complex molecular mechanisms of livestock systems in veterinary science.

Having played important roles in human growth and development, livestock animals are regarded as integral parts of society. However, industrialization has depleted natural resources and exacerbated climate change worldwide, spurring the emergence of various diseases that reduce livestock productivity. Meanwhile, a growing human population demands sufficient food to meet their needs, necessitating innovations in veterinary sciences that increase productivity both quantitatively and qualitatively. We have been able to address various challenges facing veterinary and farm systems with new scientific and technological advances, which might open new opportunities for research. Recent breakthroughs in multi-omics platforms have produced a wealth of genetic and genomic data for livestock that must be converted into knowledge for breeding, disease prevention and management, productivity, and sustainability. Vetinformatics is regarded as a new bioinformatics research concept or approach that is revolutionizing the field of veterinary science. It employs an interdisciplinary approach to understand the complex molecular mechanisms of animal systems in order to expedite veterinary research, ensuring food and nutritional security. This review article highlights the background, recent advances, challenges, opportunities, and application of vetinformatics for quality veterinary services.

Designing multi-epitope-based vaccine targeting surface immunogenic protein of Streptococcus agalactiae using immunoinformatics to control mastitis in dairy cattle.

BACKGROUND: Milk provides energy as well as the basic nutrients required by the body. In particular, milk is beneficial for bone growth and development in children. Based on scientific evidence, cattle milk is an excellent and highly nutritious dietary component that is abundant in vitamins, calcium, potassium, and protein, among other minerals. However, the commercial productivity of cattle milk is markedly affected by mastitis. Mastitis is an economically important disease that is characterized by inflammation of the mammary gland. This disease is frequently caused by microorganisms and is detected as abnormalities in the udder and milk. Streptococcus agalactiae is a prominent cause of mastitis. Antibiotics are rarely used to treat this infection, and other available treatments take a long time to exhibit a therapeutic effect. Vaccination is recommended to protect cattle from mastitis. Accordingly, the present study sought to design a multi-epitope vaccine using immunoinformatics. RESULTS: The vaccine was designed to be antigenic, immunogenic, non-toxic, and non-allergic, and had a binding affinity with Toll-like receptor 2 (TLR2) and TLR4 based on structural modeling, docking, and molecular dynamics simulation studies. Besides, the designed vaccine was successfully expressed in E. coli. expression vector (pET28a) depicts its easy purification for production on a larger scale, which was determined through in silico cloning. Further, immune simulation analysis revealed the effectiveness of the vaccine with an increase in the population of B and T cells in response to vaccination. CONCLUSION: This multi-epitope vaccine is expected to be effective at generating an immune response, thereby paving the way for further experimental studies to combat mastitis.

Investigating Multi-Target Antiviral Compounds by Screening of Phytochemicals From Neem (Azadirachta indica) Against PRRSV: A Vetinformatics Approach.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a global health problem for pigs. PRRSV is highly destructive and responsible for significant losses to the swine industry. Vaccines are available but incapable of providing adequate and long-term protection. As a result, effective and safe strategies are urgently needed to combat the virus. The scavenger receptor cysteine-rich domain 5 (SRCR5) in porcine CD163, non-structural protein 4 (Nsp4), and Nsp10 are known to play significant roles in PRRSV infection and disease development. Therefore, we targeted these proteins to identify multi-target antiviral compounds. To identify potent inhibitors, molecular docking of neem phytochemicals was conducted; three compounds [7-deacetyl-7-oxogedunin (CID:1886), Kulactone (CID:15560423), and Nimocin (CASID:104522-76-1)] were selected based on the lowest binding energy and multi-target inhibitory nature. The efficacy and safety of the selected compounds were revealed through the pharmacokinetics analysis and toxicity assessment. Moreover, 100 ns molecular dynamics (MD) simulation was performed to evaluate the stability and dynamic behavior of target proteins and their docked complexes with selected compounds. Besides, molecular mechanics Poisson-Boltzmann surface area method was used to estimate the binding free energy of each protein-ligand complex obtained from the MD simulations and validate the affinities of selected compounds to target proteins. Based on our analysis, we concluded that the identified multi-target compounds can be utilized as lead compounds for the development of natural drugs against PRRSV. If further validated in clinical studies, these compounds can be used individually or in combination against the virus.

Unraveling structural and conformational dynamics of DGAT1 missense nsSNPs in dairy cattle.

Cattle are domestic animals that have been nourishing humans for thousands of years. Milk from cattle represents a key source of high-quality protein, fat, and other nutrients. The nutritional value of milk and dairy products is closely associated with the fat content, providing up to 30% of the total fat consumed in the human diet. The fat content in cattle milk represents a major concern for the scientific community due to its association with human health. The relationship between milk fat content and diacylglycerol o-acyltransferase 1 gene (DGAT1) is well described in literature. Several studies demonstrated the difference in fat contents and other milk production traits in a wide range of cattle breeds, to be associated with missense non-synonymous single nucleotide polymorphisms (nsSNPs) of the DGAT1 gene. As a result, an nsSNPs analysis is crucial for unraveling the DGAT1 structural and conformational dynamics linked to milk fat content. DGAT1-nsSNPs are yet to be studied in terms of their structural and functional impact. Therefore, state-of-the-art computational and structural genomic methods were used to analyze five selected variants (W128R, W214R, C215G, P245R, and W459G), along with the wild type DGAT1. Significant structural and conformational changes in the variants were observed. We illustrate how single amino acid substitutions affect DGAT1 function, how this contributes to our understanding of the molecular basis of variations in DGAT1, and ultimately its impact in improving fat quality in milk.

Structural insights into inhibition of PRRSV Nsp4 revealed by structure-based virtual screening, molecular dynamics, and MM-PBSA studies.

BACKGROUND: Porcine reproductive and respiratory syndrome respiratory sickness in weaned and growing pigs, as well as sow reproductive failure, and its infection is regarded as one of the most serious swine illnesses worldwide. Given the current lack of an effective treatment, in this study, we identified natural compounds capable of inhibiting non-structural protein 4 (Nsp4) of the virus, which is involved in their replication and pathogenesis. RESULTS: We screened natural compounds (n = 97,999) obtained from the ZINC database against Nsp4 and selected the top 10 compounds for analysing protein-ligand interactions and physicochemical properties. The five compounds demonstrating strong binding affinity were then subjected to molecular dynamics simulations (100 ns) and binding free energy calculations. Based on analysis, we identified four possible lead compounds that represent potentially effective drug-like inhibitors. CONCLUSIONS: These methods identified that these natural compounds are capable of inhibiting Nsp4 and possibly effective as antiviral therapeutics against PRRSV.

Virtual screening, molecular dynamics and binding energy-MM-PBSA studies of natural compounds to identify potential EcR inhibitors against Bemisia tabaci Gennadius.

Whitefly (Bemisia tabaci Gennadius) is a hemipteran phyto polyphagous sucking insect pest which is an important pest of cotton that causes economic losses to the crop by reducing its yield and quality. Ecdysteroids such as 20-hydroxy ecdysone (20-E), play a significant role in larval moulting, development, and reproduction in pterygota insects. Receptor of 20-E, that is Ecdysone Receptor (BtEcR) of Bemisia tabaci has been targeted to prevent fundamental developmental processes. To identify potent inhibitors of BtEcr, 98,072 natural compounds were retrieved from ZINC database. A structure-based virtual screening of these compounds was performed for evaluating their binding affinity to BtEcR, and top two compounds (ZINC08952607 and ZINC04264850) selected based on lowest binding energy. Molecular dynamics simulation (MDS) study was performed for analyzing the dynamics and stability of BtEcR and top-scoring ligand-BtEcR complexes at 50 ns. Besides, g_mmpbsa tool was also used to calculate and analyse the binding free energy of BtEcR-ligand complexes. Compounds ZINC08952607 and ZINC04264850 had shown a binding free energy of -170.156 kJ mol-1 and -200.349 kJ mol-1 in complex with BtEcR respectively. Thus, these compounds can be utilized as lead for the development of environmentally safe insecticides against the whitefly.

Chemo-informatics guided study of natural inhibitors targeting rho GTPase: a lead for treatment of glaucoma.

Glaucoma, the most perilous disease leading to blindness is a result of optical neuropathy. Accumulation of aqueous humor in the posterior chamber due to a large difference in the rate of formation and its drainage in the anterior chamber causes an increase in intraocular pressure (IOP) leading to damage of nerve cells. A literature survey has revealed that inhibition of the Rho guanosine triphosphatases (rho GTPase) pathway by specific inhibitors leads to the relaxation of contractile cells involved in the aqueous outflow pathway. Relaxation of the strained contractile cells results in increased outflow thereby releasing IOP. In the present study molecular docking has been used to screen twenty seven bioactive (17 natural compounds and 10 conventional drugs) compounds that may play a significant role in relaxing contractile cells by inhibiting rho-GTPase protein. Docking results showed that among all-natural bioactive compounds Cyanidin and Delphinidine have a good binding affinity (- 8.4 kcal/mol) than the top screened conventional drug molecule Mitomycin, (- 6.3 kcal/mol) when docked with rho-GTPase protein. Cyanidin and Delphinidin belong to anthocyanidin, a glycoside form of anthocyanins from Vaccinium myrtillus L. and Punica granatum. The resembling potential of Cyanidin and Delphinidin concerning the drug Mitomycin was confirmed through simulation analysis. Molecular dynamics study (MDS) for 100 ns, showed that the rho GTPase-Delphinidine complex structure was energetically more stable than rho GTPase-Cyaniding complex in comparison to rho GTPase-Mitomycin complex. The comparative study of both the selected hits (Cyanidin and Delphinidin) was assessed by RMSD, RMSF, Rg, SASA, H-bond, PCA MM/PBSA analysis. The analysis revealed that Delphinidine is more potent to inhibit the rho GTPase as compare to Cyaniding and available conventional drugs in terms of stability and binding free energy. Based on the results, these molecules have good pharmacokinetic and pharmacodynamics properties and will prove to be a promising lead compound as a future drug for Glaucoma.

Computational analysis of microarray data of Arabidopsis thaliana challenged with Alternaria brassicicola for identification of key genes in Brassica.

BACKGROUND: Alternaria blight, a recalcitrant disease caused by Alternaria brassicae and Alternaria brassicicola, has been recognized for significant losses of oilseed crops especially rapeseed-mustard throughout the world. Till date, no resistance source is available against the disease; hence, plant breeding methods cannot be used to develop disease-resistant varieties. Therefore, in the present study, efforts have been made to identify resistance and defense-related genes as well as key components of JA-SA-ET-mediated pathway involved in resistance against Alternaria brasscicola through computational analysis of microarray data and network biology approach. Microarray profiling data from wild type and mutant Arabidopsis plants challenged with Alternaria brassicicola along with control plant were obtained from the Gene Expression Omnibus (GEO) database. The data analysis, including DEGs extraction, functional enrichment, annotation, and network analysis, was used to identify genes associated with disease resistance and defense response. RESULTS: A total of 2854 genes were differentially expressed in WT9C9; among them, 1327 genes were upregulated and 1527 genes were downregulated. A total of 1159 genes were differentially expressed in JAM9C9; among them, 809 were upregulated and 350 were downregulated. A total of 2516 genes were differentially expressed in SAM9C9; among them, 1355 were upregulated and 1161 were downregulated. A total of 1567 genes were differentially expressed in ETM9C9; among them, 917 were upregulated and 650 were downregulated. Besides, a total of 2965 genes were differentially expressed in contrast WT24C24; among them, 1510 genes were upregulated and 1455 genes were downregulated. A total of 4598 genes were differentially expressed in JAM24C24; among them, 2201 were upregulated and 2397 were downregulated. A total of 3803 genes were differentially expressed in SAM24C24; among them, 1819 were upregulated and 1984 were downregulated. A total of 4164 genes were differentially expressed in ETM24C24; among them, 1895 were upregulated and 2269 were downregulated. The upregulated genes of Arabidopsis thaliana were mapped and annotated with CDS sequences of Brassica rapa obtained from PlantGDB database. Additionally, PPI network of these genes were constructed to investigate the key components of hormone-mediated pathway involved in resistance during pathogenesis. CONCLUSION: The obtained information from present study can be used to engineer resistance to Alternaria blight caused by Alternaria brasscicola through molecular breeding or genetic manipulation-based approaches for improving Brassica oilseed productivity.

In silico identification of mimicking molecule(s) triggering von Willebrand factor in human: a molecular drug target for regulating coagulation pathway.

Blood coagulation is a complex and dynamic process wherein the body activates its emergency mechanism to stop bleeding and wound healing via the interactions of prothrombotic and antithrombotic agents. von Willebrand factor (VWF) is a complex glycoprotein and initial component of the hemostasis pathway which serves a multipurpose role in blood coagulation process. There are reports of various plants that contain several bioactive compounds possessing properties of inducing blood coagulation directly or indirectly. In the present study, efforts have been made to identify bioactive compounds that may play a significant role in regulation of the coagulation cascade by accelerating VWF and thus enhance the hemostasis process. An antidiuretic peptide drug, Desmopressin, works on VWF and releases them in circulation. Forty-seven compounds from different plant sources were screened through molecular docking, out of which two compounds, Emodin and Peruvianoside II, showed more binding affinity than the reference drug Desmopressin. Emodin and Peruvianoside II showed binding energies -7.2 and -7.0 kcal/mol, respectively, when docked with VWF, whereas Desmopressin displayed less binding energy (-6.9 kcal/mol). Emodin belongs to anthraquinone from Rumex hastasus and Peruvianoside II belongs to flavanone glycosides from Thevetia peruviana. The mimicking potential of top identified molecules with respect to the drug was confirmed through simulation analysis. Besides, the molecular dynamics simulation (MDS) study (for 20 ns) showed that the Peruvianoside II protein complex was energetically more stable than Emodin protein complex. Based on the results, Peruvianoside II possesses great potential and thus may be considered for development of drugs for hemostasis.

Correction to: Transcriptome-wide identification of genes involved in Ascorbate-Glutathione cycle (Halliwell-Asada pathway) and related pathway for elucidating its role in antioxidative potential in finger millet (Eleusine coracana (L.)).

[This corrects the article DOI: 10.1007/s13205-018-1511-9.].

Transcriptome-wide identification of genes involved in Ascorbate-Glutathione cycle (Halliwell-Asada pathway) and related pathway for elucidating its role in antioxidative potential in finger millet (Eleusine coracana (L.)).

Finger millet is being recognized as a potential future crop due to their nutrient contents and antioxidative properties, which are much higher compared to the other minor millets for providing health benefits. The synthesis of these nutritional components is governed by the expression of several gene(s). Therefore, it is necessary to characterize these genes for understanding the molecular mechanisms behind de novo synthesis of nutrient components. Apart from this, these important compounds could also serve as candidate genes for imparting stress tolerance in other crop plants also. In the present study, effort has been made to identify genes involved in Ascorbate-Glutathione cycle (Halliwell-Asada Pathway) and related pathway genes for elucidating its role in antioxidative potential mechanism through transcriptome data analysis. APX, DHAR, MDHAR, GR, and SOD have been identified as the key genes of the pathway in two genotypes GP-1 (low Ca2+) and GP-45 (high Ca2+) of finger millet with reference to rice as a model system, besides, 30 putatively expressed genes/proteins were also investigated. Furthermore, the sequences of identified genes were analyzed systematically; gene ontology (GO) annotation and enrichment analysis of assembled unitranscripts were also performed using Blast2GO. As a result, 49 GO terms, 5 Enzyme Commission (EC) numbers, and 2 KEGG pathway maps were generated. GO results revealed that these genes are mainly involved in two biological processes (BP), viz., oxidation-reduction process (GO:0055114) and cellular oxidant detoxification (GO:0098869), and showed oxidoreductase activity (GO:0016491). KEGG analysis showed that APX, DHAR, MDHAR, and GR are directly connected to biosynthetic pathways of secondary metabolites, mainly polyphenolic compounds (flavonoid, tannin, and lignin) involved in glutathione metabolism (KEGG:00480) and ascorbate and aldarate metabolism (KEGG:00053). While SOD, is indirectly connected and also has significant medicinal attributes and antioxidant properties. Moreover, Fragments Per Kilobase of transcript per Million mapped reads (FPKM) values were also calculated for expression analysis and found that the FPKM values of genes present in GP-1 are higher than that of GP-45. Thus, GP-1 genotype was found to have higher stress regulated gene expression in comparison to GP-45. Taken together, the present transcriptome-based investigation unlocks new avenues for systematic functional analysis of novel ROS scavenging candidate genes that could be effectively applied for improvising human health and nutrition.

Augmentation of crop productivity through interventions of omics technologies in India: challenges and opportunities.

With the continuous increase in the population of developing countries and decline of natural resources, there is an urgent need to qualitatively and quantitatively augment crop productivity by using new tools and technologies for improvement of agriculturally important traits. The new scientific and technological omics-based approaches have enabled us to deal with several issues and challenges faced by modern agricultural system and provided us novel opportunities for ensuring food and nutritional security. Recent developments in sequencing techniques have made available huge amount of genomic and transcriptomic data on model and cultivated crop plants including Arabidopsis thaliana, Oryza sativa, Triticum aestivum etc. The sequencing data along with other data generated through several omics platforms have significantly influenced the disciplines of crop sciences. Gene discovery and expression profiling-based technologies are offering enormous opportunities to the scientific community which can now apply marker-assisted selection technology to assess and enhance diversity in their collected germplasm, introgress essential traits from new sources and investigate genes that control key traits of crop plants. Utilization of omics science and technologies for crop productivity, protection and management has recently been receiving a lot of attention; the majority of the efforts have been put into signifying the possible applications of various omics technologies in crop plant sciences. This article highlights the background of challenges and opportunities for augmentation of crop productivity through interventions of omics technologies in India.

Systems biology of seeds: decoding the secret of biochemical seed factories for nutritional security.

Seeds serve as biochemical factories of nutrition, processing, bio-energy and storage related important bio-molecules and act as a delivery system to transmit the genetic information to the next generation. The research pertaining towards delineating the complex system of regulation of genes and pathways related to seed biology and nutrient partitioning is still under infancy. To understand these, it is important to know the genes and pathway(s) involved in the homeostasis of bio-molecules. In recent past with the advent and advancement of modern tools of genomics and genetic engineering, multi-layered 'omics' approaches and high-throughput platforms are being used to discern the genes and proteins involved in various metabolic, and signaling pathways and their regulations for understanding the molecular genetics of biosynthesis and homeostasis of bio-molecules. This can be possible by exploring systems biology approaches via the integration of omics data for understanding the intricacy of seed development and nutrient partitioning. These information can be exploited for the improvement of biologically important chemicals for large-scale production of nutrients and nutraceuticals through pathway engineering and biotechnology. This review article thus describes different omics tools and other branches that are merged to build the most attractive area of research towards establishing the seeds as biochemical factories for human health and nutrition.

Identification of new drug-like compounds from millets as Xanthine oxidoreductase inhibitors for treatment of Hyperuricemia: A molecular docking and simulation study.

Xanthine oxidoreductase plays an important role in formation of uric acid and its regulation during purine catabolism. Uncontrolled expression of this enzyme is responsible for overproduction and deposition of uric acid in blood that is potentially injurious because it can breakdown DNA and protein molecules, triggering many diseases. Human Xanthine oxidoreductase (HsXOR) is considered to be a pharmacological target for the treatment of hyperuricemia. Many of the HsXOR-inhibitor drugs such as Febuxostat and Allopurinol are known to have significant adverse effects. Therefore, there is an urgent need to develop new HsXOR-inhibitor drugs with less or no toxicity for the long-term treatment or prevention of hyperuricemia-related diseases. Many nutritious and medical functions have been reported in millets. Present work deals with identification of millet derived compounds in terms of their interaction with target, HsXOR through molecular docking and dynamic simulation studies. Of thirty two chosen compounds, Luteolin and Quercitin showed more binding affinity with HsXOR than reference drugs, Febuxostat and Allopurinol. Molecular dynamics simulations (20 ns long) revealed that Luteolin-protein complex was energetically more stable than Quercitin-protein complex. The millet derived compounds i.e. Luteolin and Quercitin showed binding energy -9.7 kcal/mol whereas the known drugs i.e. Febuxostat and Allopurinol showed binding energy -8.0 kcal/mol and -5.5 kcal/mol respectively. Based on the study, Luteolin possess high potential to be considered for trial as an inhibitor of HsXOR as it may regulate the pathway by inhibiting HsXOR. Further investigations are proposed to consider Luteolin for developing future drugs from millets and other natural sources.