PatchDock Server Research Articles

Screening miRNAs to Hinder the Tumorigenesis of Renal Clear Cell Carcinoma Associated with KDR Expression.

This study delved into the role of Kinase Insert Domain Receptor (KDR) and its associated miRNAs in renal cell carcinoma through an extensive computational analysis. The potential of our findings to guide future research in this area is significant. Our methods, which included the use of UALCAN and GEPIA2 databases, as well as miRDB, MirDIP, miRNet v2.0, miRTargetLink, MiEAA v2.1, TarBase v8.0, INTERNET, and miRTarBass, were instrumental in identifying the regulation of miRNA associated with KDR expression. The predicted miRNA was validated with the TCGA-KIRC patients' samples by implementing CancerMIRNome. The TargetScanHuman v8.0 was implemented to identify the associations between human miRNAs and KDR. A Patch Dock server analyzed the interactions between hsa-miR-200b-3p-KDR and hsa-miR-200b-3p with KDR. The KDR expression rate was investigated in the Kidney Renal Cell Carcinoma (KIRC) samples, and adjacent normal tissues revealed that the expression rate was significantly higher than the normal samples, which was evident from the strong statistical significance (P = 1.63e-12). Likely, the KDR ex-pression rate was estimated as high at tumor grade 1 and gradually decreased till the metastasis grade, reducing the survival rate of the KIRC patients. To identify these signals early, we predicted a miRNA that could trigger the expression of KDR. Furthermore, we uncovered the potential associations between miR-200c-3p expressions by regulating KDR towards the progression of KIRC. Upon examining the outcome, it became evident that miR-200c-3p was significantly down-regulated in KIRC compared to the normal samples. Moreover, the negative correlation was obtained for hsa-miR-200c-3p (R = - 0.276) along with the KDR expression describing that the increased rate of hsa-miR-200c-3p might reduce the KDR expression rate, which may suppress the KIRC initiation or progres-sion. The in-silico analysis indicated that the significant increase in KDR expression during the initiation of KIRC could serve as an early diagnostic marker. Moreover, KDR could be utilized to identify advancements in KIRC stages. Additionally, hsa-miR-200c-3p was identified as a potential regulator capable of downregulating and upregulating KDR expression among the 24 miRNAs screened. This find-ing holds promise for future research endeavors. Concurrent administration of the FDA-approved 5-fluor-ouracil with KIRC drugs, such as sorafenib, zidovudine, and everolimus, may have the potential to en-hance the therapeutic efficacy in downregulating hsa-miR-200c-3p. However, further in vitro studies are imperative to validate these findings and gain a comprehensive understanding of the intricate regulatory interplay involving hsa-miR-200c-3p, KDR, 5-fluorouracil, and other FDA-approved drugs for the treat-ment of KIRC. This will facilitate the identification of KIRC stage progression and its underlying pre-ventative mechanisms.

2-Propyl-1H-imidazole-4,5-dicarboxylate acid supported cu/ni/fe/co complexes: synthesis, biological and catalytic evaluation

Herein, we report 2-propyl-1H-imidazole-4,5-dicarboxylate complexes of Cu/Co/Fe/Ni metal ions. The complexes have been characterized using powder X-ray diffraction, FTIR, and mass spectrometry. Thermal gravimetric analysis (TGA) established their thermal stability, enduring temperatures of up to 650 °C. The interaction of Bovine Serum Albumin (BSA) and DNA with these complexes was examined, revealing a significant binding affinity up to 70%. Fluorescence quenching experiments also showed the binding of complexes with biomolecules. These interactions were substantiated by molecular docking studies against the proteins 3v03 (BSA) and 1d28 (DNA), shedding light on the essential interactions driving their potential medicinal activity. The Cu complex displayed a notably high GSC score and a substantial area as determined through the Patch Dock server. Free radical interaction with 2,2-diphenylpicrylhydrazyl (DPPH) shows their antioxidant activity where Cu and Fe complexes expressed greater activity as compared to others. The catalytic properties of the compounds were assessed using p-nitrophenol (PNP) where the complexes exhibited reducing activity, leading to a conversion of over 90% of PNP into p-aminophenol. Analysis revealed a pseudo-second-order model closely aligned with experimental values, indicating second-order reduction kinetics.

Exploring Neophytadiene from Ampelocissus araneosa: A Molecular Docking Approach to Inhibit Biofilm Formation in Staphylococcus aureus

Background: The urgent need to combat antimicrobial resistance and biofilm production has prompted the exploration of alternative remedies, such as plant extracts, as viable substitutes for antibiotics.
 Aim: This study aims to assess the phytocompound from A. araneosa and elucidate its inhibitory mechanisms against biofilm formation by S. aureus through molecular docking techniques.
 Methodology: Plant material collection and extract preparation were conducted, followed by GCMS analysis of A. araneosa and protein modeling of Biofilm_IcaR from S. aureus. Drug 3D prediction and drug docking studies were performed using Neophytadiene and Metronidazole, with the Patch Dock server for the exploration of molecular interactions between the compounds and protein targets.
 Results and Implications: The study identified bioactive compounds from A. araneosa, including neophytadiene, 3-eicosyne, phytol, and stigmasterol, known for their robust antimicrobial properties. Molecular docking studies demonstrated that neophytadiene exhibited a higher binding affinity to the Biofilm_IcaR protein compared to the control drug, Metronidazole, suggesting its efficacy as an inhibitor. These findings provide molecular insights into the potential of neophytadiene as a therapeutic agent against biofilm-producing S. aureus, with implications for the development of novel antimicrobial treatments.

Designing Drug Delivery Vehicles based on N-(2-Hydroxypropyl) Methacrylamide.

The development of polymeric-based drug delivery has seen faster growth in the past two decades. In polymers, copolymers as drug carriers are increasing to decrease the drug compounds' side effects and dosage-related toxicity. The study's primary objective is to utilize computational resources to design drug molecules and perform in silco physicochemical property analysis. In our study, we designed new copolymers based on N-(2-Hydroxypropyl) methacrylamide (HPMA) as backbone along with polyethylene glycol (PEG) and lauryl methacrylate (LMA). Different functional groups were selected for attaching to the side chain of the copolymers through a random trial and error approach. In order to predict the pharmacokinetic properties (absorption, distribution, metabolism, excretion, and toxicity), the designed copolymer molecules were evaluated utilizing ADME and PkCSM pharmacokinetics servers. Molecular interaction between the designed copolymer molecules and human serum albumin (HSA) was performed using AutoDock Vina and PatchDock server. The designed molecules are shown to be soluble in water and have high gastrointestinal absorption. Only one molecule is predicted to pass through the blood-brain barrier. Two designed molecules have been shown to have carcinogenic properties. Lethal dose 50 (LD50), cytochrome P450, and permeability glycoprotein Enzyme's substrate formation were also analyzed for toxicity and metabolism. Our study will provide insight for designing new drug compounds or carriers and analyzing their physicochemical properties to help further optimize compounds for clinical studies.

Computational screening of foxtail millet (Setaria italica (L.) P.Beauv.) polyphenols for finding β-secretase (BACE 1) inhibitors that target the amyloidogenic pathway in Alzheimer's disease

Abstract BACKGROUND: Foxtail millet (FM; Setaria italica (L.) P.Beauv.) is known for its antioxidant and neuroprotective action against Alzheimer's disease (AD); hence the present study aims to screen its polyphenols to find less toxic and potentially effective anti-Alzheimer's drugs. MATERIALS AND METHODS: The details about phyto-compounds of FM and the β-secretase enzyme (BACE 1) of AD have been retrieved from the PubChem compound database and protein data bank, respectively. The Patch Dock server was used to carry out docking experiments. Initially, all the FM phytocompounds and reference drug (MK-8931) were subjected to docking, and subsequently, the best-docked complexes were selected based on their binding energy (in kcal/mol). Rule of five and adsorption, distribution, metabolism, excretion, and toxicity (ADMET) of selected compounds were analyzed using various computational tools. The final docking complexes were developed by using PyMOL. RESULTS: The molecular docking results revealed that among the 24 polyphenols studied, two compounds, namely N′-p-coumaroyl-N″-caffeoylspermidine (NPCNCS) and di-P-coumaroylspermidine (DPCS), demonstrated strong binding to the active site of β-secretase. and exhibited higher binding energies of -300.75 kcal/mol and -193.41 kcal/mol, respectively, in comparison to the reference drug MK-8931, with a binding energy of -154.36 kcal/mol. These compounds established hydrogen bond interactions with catalytic dyad (Asp 32 and Asp 228) and other accessory interactions with residues of the “flap” hairpin loop and “10s loop” of the β-secretase active site involved in the stabilization of substrate/inhibitor binding. In a nutshell, the NPCNCS and DPCS have shown more robust binding affinity than MK-8931 and docked well into the interior side of the active site. On the other hand, NPCNCS and DPCS have satisfied the RO5 and ADMET filters. CONCLUSIONS: The in silico analysis of FM polyphenols revealed that the N′-p-coumaroyl-N″-feruloylspermidine and di-P-coumaroylspermidine compounds exhibited non-toxic, permeability to blood-brain barrier and solid binding affinity toward β-secretase enzyme thereby; these millet compounds might be considered as β-secretase inhibitors for treating AD.

IN-SILICO ANALYSIS OF THYMOQUINONE AS AN ANTI-CANCER AGENT AGAINST CHEMORESISTANCE-ASSOCIATED PROTEINS IN OVARIAN CANCER

Thymoquinone (TQ), a polyphenol obtained from Nigella sativa plays a fundamental role in controlling homeostasis. Itpossesses anti-cancer, anti-oxidant, anti-inflammatory, and analgesic properties. Its anti-cancer properties extend tolymphoma, leukaemia, medulloblastoma, prostate, pancreatic, breast, and ovarian cancer (OvCa). OvCa is one of themost lethal malignancies worldwide having distinct symptoms and a poor prognosis. Resistance to Cisplatin (CDDP) andsubsequent reoccurrence of tumors lead to treatment failure. To tackle this, combination therapies along withpolyphenols are being studied and have been proven to enhance CDDP response. Certain proteins such as Bcl-2, Bax,STAT3, p53, and caspase-3/9 are involved in cancer progression and signaling of chemoresistance. In this study,Thymoquinone (TQ) interactions with these proteins have been observed through molecular docking. The 3D structureprediction was carried out using Phyre2 and SWISS-MODEL. The molecular docking of protein targets and TQ wasdone using the PatchDock server. The docked results were then visualized using Discovery Studio. This study helps us tounderstand the interactions between TQ and apoptotic proteins that help in the augmentation of conventional therapy.This knowledge will also help in developing a new approach and alternate therapeutic strategies using polyphenols likeTQ, even in resistant cells.

Targeting Epithelial to Mesenchymal Transition in Breast Cancer with Bioactive Compounds derived from Solanum surattense: A GC-MS and Molecular Docking approach

The epithelial to mesenchymal transition (EMT) has been associated with the invasion and migration of tumor cells, thus playing a fundamental role in cancer progression and metastasis. Breast cancer is a heterogeneous disease, which has been regarded as one of the leading causes of death amongst women globally. The initiation of EMT in breast cancer embraces the involvement of multiple signaling pathways. The involvement of a few factors present in EMT has left a prominent impact on shaping breast cancer development. Solanum surattense, belonging to the family Solanaceae, possesses numerous therapeutic properties due to the presence of several substances. In this study, we focused on major key players genes in promoting EMT, which increases the severity of cancer. Using GC/MS analysis, the active compounds from Solanum surattense were predicted. Molecular docking studies for this extracted active compounds were performed against the genes responsible for EMT using the PatchDock server. The docked complexes were then visualized using PyMOL. Results obtained from the molecular docking showed the inhibitory effect against the EMT pathway, thus inhibiting breast cancer progression.

In Silico Discovery of GPCRs and GnRHRs as Novel Binding Receptors of SARS-CoV-2 Spike Protein Could Explain Neuroendocrine Disorders in COVID-19.

Despite the intense research work since the beginning of the pandemic, the pathogenesis of COVID-19 is not yet clearly understood. The previous mechanism of COVID-19, based on ACE2 tropism and explained through a single receptor, is insufficient to explain the pathogenesis due to the absence of angiotensin-converting enzyme 2 (ACE2) receptors in most of the affected organs. In the current study, we used the PatchDock server to run a molecular docking study of both the gonadotropin-releasing hormone receptor (GnRHR) and G-protein-coupled-receptor (GPCR) with the SARS-CoV-2 spike protein. Molecular Dynamics (MD) simulations were run to analyze the stability of the complexes using the GROMACS package. The docking results showed a high affinity between the spike protein with the GnRHR (−1424.9 kcal/mol) and GPCR (−1451.8 kcal/mol). The results of the MD simulations revealed the significant stability of the spike protein with the GnRHR and GPCR up to 100 ns. The SARS-CoV-2 spike protein had strong binding interactions with the GPCRs and GnRHRs, which are highly expressed in the brain, endocrine organs, and olfactory neurons. This study paves the way towards understanding the complex mechanism of neuroendocrine involvement and peripheral organ involvement, may explain the changing symptoms in patients due to new variants, and may lead to the discovery of new drug targets for COVID-19. In vitro studies involving genetic engineering or gene knockdown of the GPCRs and GnRHRs are needed to further investigate the role of these receptors in COVID-19 pathogenesis.

Chemical Profile of Value-added Oyster Mushrooms

>The human corona virus disease of 2019 is a viral disease that can produce oxidative stress due to reduced antioxidant activity. Black cumin is a plant that can be taken as a supplement to boost antioxidant levels in the body, although the process is still unknown. As a result, the in silico method will be used to screen the potential of Nigella sativa peptide as an antioxidant in this study. Protein tracking was done using the UniProt database, with KEAP1 as the target protein (GDP: 5CGJ). Molecular docking was performed using Patchdock Server and antioxidant activity was determined using https://services.healthtech.dtu.dk/service.php?AnOxPePred-1.0. The researchers concluded that peptides found in N. sativa’s NAD(P)H-quinone oxidoreductase subunit 5, chloroplastic protein, had antioxidant potential through suppressing KEAP1 activity with the lowest ACE in Tyr-Tyr-Glu and Cys-Tyr-Tyr.

Point mutation consideration in CcO protein of the electron transfer chain by MD simulation

In Acidithiobacillus ferrooxidans, proteins such as CcO are present in the electron transport pathway. They cause ferrous iron oxidation to ferric leading to the electron release. CcO has two copper atoms (CuA, CuB). CuA plays an important role in electron transfer. According to previous studies, the conversion of histidine to methionine in a similar protein increased the redox potential and was directly related to the number of electrons received. Also, the binding of methionine 233 to CuA and CuB in the wild protein structure is the reason for the selection of the H230 M mutation in the CuA site. Then, wild-type and H230 M mutant were simulated in the presence of a bilayer membrane POPC using the gromacs version 5.1.4. The changes performed in the H230 M mutant were evaluated by MD simulations analyzes. CcO and CoxA proteins are the last two proteins in the chain and were docked by the PatchDock server. By H230 M mutation, the connection between CuA and M230 weakens. The M230 moves further away from CuA, resulting become more flexible. Therefore, the Methionine gets closer to E149 of the CoxA leading to the higher stability of the CcO/CoxA complex. The results of RMSF analysis at the mutation point showed a significant increase. This indicates more flexibility in the active site. And leads to an increase in E0 in the mutation point, an increase in the rate of electron reception, and an improved bioleaching process.

In Silico Study: Combination of α-Mangostin and Chitosan Conjugated with Trastuzumab against Human Epidermal Growth Factor Receptor 2.

Breast cancer is a type of cancer with the highest prevalence worldwide. Almost 10–30% of breast cancer cases are diagnosed as positive for HER2 (human epidermal growth factor receptor 2). The currently available treatment methods still exhibit many shortcomings such as a high incidence of side effects and treatment failure due to resistance. This in silico study aims to simulate α-mangostin and chitosan combination conjugated to trastuzumab formulation against HER2 as an effort to improve breast cancer patient therapy. This molecular docking simulation was done through using PatchDock Server. The materials used including the two-dimensional structure of α-mangostin, chitosan, and sodium tripolyphosphate from the PubChem database; trastuzumab FASTA sequence from the DrugBank database; and HER2 structure obtained from a crystal complex with PDB ID: 1N8Z. The results indicated that the particle of α-mangostin and chitosan combinations interacted mostly with the crystallizable fragment (Fc region) of trastuzumab in the conjugation process. The conjugation of trastuzumab to the particle of a combination of α-mangostin and chitosan resulted in the greatest increase in the binding score of the smallest-sized particles (50 Å) with an increase in the score of 3828 and also gave the most similar mode of interaction with trastuzumab. However, the conjugation of trastuzumab eliminated the similarity of the mode of interaction and increased the value of atomic contact energy. Thus, a cominbation of α-mangostin and chitosan conjugated to a trastuzumab formulation was predicted can increase the effectiveness of breast cancer therapy at a relatively small particle size but with the consequence of decreasing atomic contact energy.

A foundational theoreticalAl12E12(E = N, P) adsorption and quinolone docking study: cage–quinolone pairs, optics and possible therapeutic and diagnostic applications

This combined Al12 E 12 (E = N, P) surface adsorption and docking study describes the new possibility of prospective potential probing(photophysical/optical) and therapy(medicinal/biochemical) with these adsorbent conjugates. DFT investigations were undertaken herein to help generate geometrical models and better understand the possible favorable adsorption energetics. We attempt to explain their adsorption behaviors and docking involving SARS–CoV–2 viruses (PDB)to assess their possible pharmaceutical potential against the pandemic virus (COVID–19). The adsorption behavior of 8–hydroxy–2–methylquinoline (MQ) and its halogenated derivatives, 5,7–diiodo–8–hydroxy–2–methylquinoline (MQI), 5,7–dichloro–8–hydroxy–2–methylquinoline (MQCl), and 5,7–dibromo–8–hydroxy–2–methylquinoline (MQBr), with aluminum–nitrogen (AlN), and aluminum–phosphorous (AlP) fullerene–like nanocages is reported. A decrease in the hardness of the nanoclusters when adsorbed with drug molecules resulted in an incrementally improved chemical softness (see e.g., Hard–Soft Acid Base theory) indicating that reactivity of the drug molecule in the resulting complex increases upon cluster chemical adsorption. The energy gap is found to be maximized for AlN–MQ and minimized for AlP–MQI; the reduced density gradient (RDG) iso–surfaces and AIM studies also corroborated this. Therefore, these two were found, respectively, to be the least and most electrically conductive of the species under study. We selected a simple medicinal building block (chelator)in addition to selecting the cluster based on previous literature reports. Important parameters such as gap energies and global indices were determined. We assessed NLO properties. The SARS–CoV–2 virus PDB docking data for 6VW1, 6VYO, 6WKQ, 7AD1, 7AOL, 7B3C, were enlisted as ligand targets for studies of docking (PatchDock Server) using the requisite PDB geometries (For the structure of 6VW1, kindly see reference, 2020; For the structure of 6VYO kindly see reference, 2020; For the structure of 6WKQ kindly see reference, 2020; For the structure of 7AD1 kindly see reference, 2021; For the structure of 7AOL kindly see reference, 2021; For the structure of 7B3C kindly see reference, 2021). Such findings indicate that the AlN–drug conjugation have inhibitory effect against these selected receptors.

Active-site molecular docking of nigellidine with nucleocapsid–NSP2–MPro of COVID-19 and to human IL1R–IL6R and strong antioxidant role of Nigella sativa in experimental rats

The recent outbreak of SARS CoV-2 has changed the global scenario of human lives/economy. A significant number of the non-survivors showed cardiac renal vasculature dysfunction. A ‘cytokine storm’ namely, interleukin IL6–IL1 receptors, i.e. IL6R–IL1R over-functioning was reported. Here, nigellidine, an indazole alkaloid and key component of Nigella sativa L. (NS) commonly known as black cumin seed was analysed for COVID-19 protein targeting and IL1R–IL6R inhibition through molecular docking study and biochemical study in experimental rat to evaluate antioxidative capacity. The NMR/X-ray crystallographic/electron microscopic structures of COVID-19 main protease (6LU7)/spike glycoprotein (6vsb)/NSP2 (QHD43415_2)/nucleocapsid (QHD43423), human IL1R (1itb)-IL6R (1pm9) from PDB were retrieved analysed for receptor–ligand interaction. Then, those structures were docked with nigellidine using AutoDock and PatchDock server. A brief comparison was made with nigellicine thymoquinone from N. sativa. Where nigellidine showed highest binding energy of −6.6 kcal/mol, ligand efficiency of −0.3 with COVID19 Nsp2 forming bonds with amino acid CYS240 present in binding pocket. Nigellidine showed strong interaction with main protease (BE: –6.38/LE: –0.29). Nigellidine showed affinity to IL1R (–6.23). The NS treated rat showed marked decline in ALP-SGPT-SGOT-malondialdehyde (MDA) than the basal levels. From the Western blot and activity analysis, it was observed that Nigellidine (sulphuryl group drug) showed no impact on phenol-catalysing ASTIV and steroid-catalysing oestrogen-sulphotransferase expressions and activities in liver tissue and thus has no influence in sulphation-mediated adverse metabolic processes. Conclusively, nigellidine has hepato-reno-protective/antioxidant-immunomodulatory/anti-inflammatory activities with inhibit potentials of COVID-19 proteins. Further validation is necessary.

Evaluation of Cyc1 protein stability in Acidithiobacillus ferrooxidans bacterium after E121D mutation by molecular dynamics simulation to improve electron transfer.

Cyc1 (Cytochrome c552) is a protein in the electron transport chain of the Acidithiobacillus ferrooxidans (Af) bacteria which obtain their energy from oxidation Fe2+ to Fe3+. The electrons are directed through Cyc2, RCY (rusticyanin), Cyc1 and Cox aa3 proteins to O2. Cyc1 protein consists of two chains, A and B. In the present study, a novel mutation (E121D) in the A chain of Cyc1 protein was selected due to electron receiving from Histidine 143 of RCY. Then, the changes performed in the E121D mutant were evaluated by MD simulations analyzes. Cyc1 and RCY proteins were docked by a Patchdock server. By E121D mutation, the connection between Zn 1388 of chain B and aspartate 121 of chain A weaken. Asp 121 gets farther from Zn 1388. Therefore, the aspartate gets closer to Cu 1156 of the RCY leading to the higher stability of the RCY/Cyc1 complex. Further, an acidic residue (Glu121) becomes a more acidic residue (Asp121) and improves the electron transfer to Cyc1 protein. The results of RMSF analysis showed further ligand flexibility in mutation. This leads to fluctuation of the active site and increases redox potential at the mutation point and the speed of electron transfer. This study also predicts that in all respiratory chain proteins, electrons probably enter the first active site via glutamate and exit histidine in the second active site of each respiratory chain protein.

Epitope Identification in BEFV N protein for Detecting Effective Points

Background & Objective: The common cause of milk production loss in cattle and water buffalo is bovine ephemeral fever (BEF). Previous cases have been reported in Iran's south regions, with a low mortality rate. As a result, studying BEFV and identifying ideal epitopes for further developing diagnostic Kit is important.
 Materials & Methods: To investigate BEFV N protein epitopes, we collected samples, extracted and sequenced DNA, and then used the ExPaSy translate method to deduce the amino acid sequence. Various immunoinformatics techniques were used to analyze physical/chemical properties, secondary structure of protein sequences, membrane topology, antigenic property, and 3D structure. BCPRED and the DiscoTope server, respectively, predicted linear and discontinuous epitopes of BEFV N protein. Finally, the PatchDock server was used to dock peptides and antibodies.
 Result: Three linear epitopes and sixteen discontinuous epitopic positions were discovered. Furthermore, molecular docking between epitopes and low-binding-energy antibodies revealed that they have easy access to the immune system.
 Conclusion: In this study, bioinformatics techniques were used to predict epitopes of the BEFV N protein for further developing BEFV diagnostic Kits and recombinant vaccines. Furthermore, experimental validation is needed for these epitopes.

Characterization and Molecular Docking Analysis for the Supramolecular Interaction of Lidocaine with β-Cyclodextrin

In the present work, Lidocaine: β-Cyclodextrin (LDC:β-CD) complex is formed and confirmed through analytical methods. The absorption and fluorescence maxima of the complex is shifted toward the blue region with the increasing concentration of β-CD. The FT-IR study predicts the entrapment of the aromatic part into the cavity of the host, as the stretching frequencies of those groups are higher than the frequencies of the pure LDC and its physically mixed (PM and KM) products. A best model is arrived through the molecular docking study with the help of Patch-Dock server for the complex formation. The cytotoxic activity of the complex is improved due to the encapsulation process and it is active toward the cancer cells even though, the pure LDC is inert to the cell line in nature.

In Silico Identification and Characterization of a Hypothetical Protein From Rhodobacter capsulatus Revealing S-Adenosylmethionine-Dependent Methyltransferase Activity

Rhodobacter capsulatus is a purple non-sulfur bacteria widely used as a model organism to study bacterial photosynthesis. It exhibits extensive metabolic activities and demonstrates other distinctive characteristics such as pleomorphism and nitrogen-fixing capability. It can act as a gene transfer agent (GTA). The commercial importance relies on producing polyester polyhydroxyalkanoate (PHA), extracellular nucleic acids, and commercially critical single-cell proteins. These diverse features make the organism an exciting and environmentally and industrially important one to study. This study was aimed to characterize, model, and annotate the function of a hypothetical protein (Accession no. CAA71016.1) of R capsulatus through computational analysis. The urf7 gene encodes the protein. The tertiary structure was predicted through MODELLER and energy minimization and refinement by YASARA Energy Minimization Server and GalaxyRefine tools. Analysis of sequence similarity, evolutionary relationship, and exploration of domain, family, and superfamily inferred that the protein has S-adenosylmethionine (SAM)-dependent methyltransferase activity. This was further verified by active site prediction by CASTp server and molecular docking analysis through Autodock Vina tool and PatchDock server of the predicted tertiary structure of the protein with its ligands (SAM and SAH). Normally, as a part of the gene product of photosynthetic gene cluster (PGC), the established roles of SAM-dependent methyltransferases are bacteriochlorophyll and carotenoid biosynthesis. But the STRING database unveiled its association with NADH-ubiquinone oxidoreductase (Complex I). The assembly and regulation of this Complex I is mediated by the gene products of the nuo operon. As a part of this operon, the urf7 gene encodes SAM-dependent methyltransferase. As a consequence of these findings, it is reasonable to propose that the hypothetical protein of interest in this study is a SAM-dependent methyltransferase associated with bacterial NADH-ubiquinone oxidoreductase assembly. Due to conservation of Complex I from prokaryotes to eukaryotes, R capsulatus can be a model organism of study to understand the common disorders which are linked to the dysfunctions of complex I.

Evaluation of selected carotenoids of Lycopersicon esculentum variants as therapeutic targets for \u2018Alzheimer\u2019s disease: an in silico approach

The seriousness and menace of the worldwide weight of ‘Alzheimer’s disease have been related to a few factors, which incorporate antioxidant system depletion, mutation of proteins, and high expression of cholinesterases due to aging, environmental influence, diet, infectious agents, and hormonal imbalance. Overexpression of cholinesterases has been emphatically connected to ‘Alzheimer’s disease because of the unreasonable hydrolysis of acetylcholine and butyrylcholine. Certain plant phytochemicals, for example, beta-carotenoids, lutein, neoxanthin, and viola-xanthine from Lycopersicon esculentum Mill. Var. esculentum (ESC) and Lycopersicon esculentum Mill. Var. cerasiforme (CER) has been utilized altogether as a therapeutic candidate for the treatment of ‘Alzheimer’s disease. Therefore, this research sought to investigate the drug-likeness of the individual carotenoids as detailed for cholinesterase inhibition in the treatment of ‘Alzheimer’s disease. Four potential cholinesterase inhibitors from ESC and CER were retrieved from the PubChem database. Investigation of their drug-likeness, toxicity prediction, molecular docking, and dynamic simulations were carried out using Molinspiration, PreADMET V.2.0, Patchdock server, and Schrodinger Maestro software respectively. Neoxanthin was ranked the safest with a greater tendency to inhibit the cholinesterases with high binding affinity. In addition, its stability after simulation in a mimicked biological environment suggests its relevance as a potential drug candidate for the treatment of ‘Alzheimer’s disease through the inhibition of cholinesterases.

PCOS Modulatory Activity of Tinospora cordifolia leaves – An Insilico Approach

The polycystic ovarian syndrome affects women of all age groupsis mainly due to hyperinsulinemia and hyperandrogenism.The insulin action in the ovaries is mediated by binding to its receptor namely IRS (Insulin receptor substrate).The present investigation is undertaken to select a suitable antagonistic ligand from the bioactive phyto components of Tinosporacordifolialeaves to inhibit IRS1 and IRS 2 receptors to prevent the binding of insulin and subsequent hyperandrogenism.The phyto ligands used for the study were obtained from the previous literature and the IRS1 and IRS 2 receptor protein structure were retrieved from PDB (protein Data bank). Using the Corina 3D converter the ligand 3D structures were obtained. Molecular docking analysis was performed through Patch dock server to select a suitable ligand based on docking score for the IRS1 and IRS 2 receptor protein.Three ligands namely Berberine, Rumphioside I and Syringin showed better docking score among the ligand selectedand their inhibitory activity were analysed by intermolecular interactions using “LIGPLOT” analysis. It can be concluded that these three ligands can be used for the successful treatment of PCOS after proper preclinical and clinical studies.

Immunoinformatics based design and prediction of proteome-wide killer cell epitopes of Leishmania donovani: Potential application in vaccine development

Despite several extensive and exhaustive efforts, search for potential therapy against leishmaniasis has not made much progress. In the present work, we have employed mining strategy to screen Leishmania donovani proteome for identification of promising vaccine candidate. We have screened 21 potential antigenic proteins from 7960 total protein of L. donovani, based on the presence of signal peptide, GPI anchor, antigenicity prediction and substractive proteomic approach. Secondly, we have also performed comprehensive immunogenic epitope prediction from the screened 21 proteins, using IEDB-AR tools. Out of the 21 antigenic proteins, we obtained 11 immunogenic epitopes from 9 proteins. The final results revealed that four predicted epitopes namely; YPAFAALVF, VAVAATVAY, AAAPTEAAL and MYPLVAVVF, have significantly better binding potential with respective alleles and could elicits immune responses. Docking analysis using PATCHDOCK server and molecular dynamic simulation using GROMACS revealed the potential of the sequences as immunogenic epitopes. In silico studies also suggested that the epitopes occupied almost same binding cleft with the respective alleles, when compared with the reference peptides. It is also suggested from the molecular dynamic simulation data that the peptides were intact in the pocket for longer periods of time. Our study was designed to select MHC class I restricted epitopes for the activation of CD8 T cells using immunoinformatics for the prediction of probable vaccine candidate against L. donovani parasites. Communicated by Ramaswamy H. Sarma