Docking Server Research Articles

An injectable self-assembling hydrogel based on RGD peptidomimetic β-sheets as multifunctional biomaterials

Ability of the cells to adhere to an extracellular material is central to successful tissue genesis. Arg-Gly-Asp (RGD) sequences found in extracellular matrix proteins are well known for cell adhesion, however, enzymatic degradation and lack of specificity have limited their widespread use. Besides, a multifunctional material with inherent antimicrobial ability would help in invigorating the practical tissue engineering applications. Here, we report novel modified RGD (MR) and RGD mimic [R(K)] peptides (MOH and MNH2) which were synthesized post-in-silico screening, based on their interactions with integrin protein αVβ3 using HEX 8.0 docking server. These mimics, containing hydrophobic Phe-Phe (FF) moiety which has been specifically introduced to initiate the self-assembling process of β-sheet structures, were characterized thoroughly using various physicochemical and spectroscopic techniques. Under physiological conditions, these mimetics displayed thixotropic behavior rendering them highly suitable as injectable hydrogels having an added advantage of site-specific targeting abilities. Electron microscopy further revealed the formation of nanofibers upon self-assembly of these peptides. Besides, enhanced cell adhesiveness by these peptides compared to the commercial Poly l-lysine coated surfaces as well as the inherent antimicrobial potential against both sensitive and antibiotic-resistant pathogens (Methicillin-resistant Staphylococcus aureus and multi-drug resistant Salmonella enteritidis) substantiated the applicability of these unique injectable hydrogels wherein the porous fibrous framework offered a favorable environment for drug entrapment and 3D cell culture. Altogether, these properties render these novel RGD mimic peptides as promising multifunctional candidates for various tissue regenerative applications.

De Novo In-silico Pharmacological Analysis of Herbal Phytoconstituents for COVID-19 Treatment

Objective: The focus is to screen the phytoconstituents of various Indian medicinal plants using virtual screening tools against various targets of COVID-19 to develop potential compound for its treatment. Methods: The phytoconstituents of many herbal plants were screened based on literature review and then subjected to drug likeness property along with its bioactivity score. Docking of screened compounds with the targets of CoV being available default in the COVID-19 Docking Server tool based on Schrodinger maestro was demonstrated. Further, the docking was analysed using PyRx and AutoDock 4.2. The phytoconstituents were then taken for ADME estimation by ADME/T tool and SwissADME tool. The toxicity was predicted utilising TEST software. Results: Out of all, eleven phytoconstituents exhibited significant molecular properties and bioactivity score. After docking all compounds using various tools, their top binding scores were tabulated. It shows that the phytoconstituents Amritoside D and Tinocordifolin effectively produces significant action against COVID-19 when compared with the standard drugs currently been used. i.e., Favipiravir and Chloroquine. Further, it exhibited better absorption and distribution parameters for Pharmacokinetics of the drug. Hence, the toxicity estimation was also predicted focusing mainly on Oral Rat LD50 values. Conclusion: From all these results, it suggests that the compounds Amritoside D and Tinocordifolin produce significant results against COVID-19. Hence, further in-vitro and clinical studies have to be performed to develop drug for CoV treatment in a speedy way.

ER/AR Multi-Conformational Docking Server: A Tool for Discovering and Studying Estrogen and Androgen Receptor Modulators.

The prediction of the estrogen receptor (ER) and androgen receptor (AR) activity of a compound is quite important to avoid the environmental exposures of endocrine-disrupting chemicals. The Estrogen and Androgen Receptor Database (EARDB, http://eardb.schanglab.org.cn/) provides a unique collection of reported ERα, ERβ, or AR protein structures and known small molecule modulators. With the user-uploaded query molecules, molecular docking based on multi-conformations of a single target will be performed. Moreover, the 2D similarity search against known modulators is also provided. Molecules predicted with a low binding energy or high similarity to known ERα, ERβ, or AR modulators may be potential endocrine-disrupting chemicals or new modulators. The server provides a tool to predict the endocrine activity for compounds of interests, benefiting for the ER and AR drug design and endocrine-disrupting chemical identification.

Scrutiny of Metal Ion Binding Sites in Different Alginate Lyases through In Silico Analysis.

Alginate lyases are epitomized as prospective therapeutic mediators for treating Pseudomonas aeruginosa infections, particularly in the cystic fibrosis airway through alginate degradation thereby improving the efficacy of anti-pseudomonal antibiotics. Investigation of metal-binding residues is significant for expounding the ion specificity of an enzyme and will provide a broad understanding of the potential roles of metal ions in enzyme function and stability. However, experimental analysis of metal ion-binding sites in proteins is time consuming and expensive. Concerning the clinical importance of this therapeutic enzyme, the present study was focused on the prediction and characterization of metal ion-binding sites of different alginate lyases reported in the literature through a computational approach using a Metal Ion-Binding Site Prediction and Docking Server. 3D structures of different alginate lyase from different organisms were retrieved, and these retrieved proteins were docked with twelve different metal ions such as Ca2+, Cu2+, Fe3+, Mg2+, Mn2+, Zn2+, Cd2+, Fe2+, Ni2+, Hg2+, Co2+, and Cu+. The binding affinity and interacting amino acids for alginate lyases produced by different microorganisms were compared and analysed. Further analysis on active site residues of reported alginate lyase and subsequent experiments will reveal the function of different metal ions in enhancing or inhibiting the catalysis of alginate lyase and will help in exploiting the enzyme as an efficient therapeutic agent as well as for industrial applications.

1, 3-THIAZOLE DERIVATIVES AS ANTIMICROBIAL AGENTS: A MOLECULAR DOCKING STUDY

Introduction: Antibacterial medications like cefditoren pivoxil, a third-generation oral formulation with broad spectrum efficacy against pathogens including gram-negative and gram-negative bacteria, frequently contain thiazole moiety. When molecules are bonded to one another to form a stable complex, molecular docking technique is used to forecast the preferred orientation of one molecule to another.
 Objective: The current study reports the use of the Ligand fit module in the docking server to perform molecular docking studies on nine 1,3 thiazole derivatives into the binding pocket of glucosamine-6-phosphate synthase (PDB Id: 1jxa).
 Results: The orientation of inhibitors bound in the active site of bacterial glucosamine-6-phosphate synthase was determined by automated docking (PDB ID 1jxa).
 Conclusion: research disclosed that N-(4-(2-benzamidothiazol-4-yl)phenyl)-N-oxohydroxylammonium (compound 1), N-(4-(2-benzamidothiazol-4-yl)phenyl)-O-fluoro-N-oxohydroxylammonium (compound 2), N-(4-(2-benzamidothiazol-4-yl)phenyl)-O-chloro-N-oxohydroxylammonium (compound 3), N-(4-(2-benzamidothiazol-4-yl)phenyl)-O-iodo-N-oxohydroxylammonium (compound 5) & O-amino-N-(4-(2-benzamidothiazol-4-yl)phenyl)-N-oxohydroxylammonium (compound 6) have high antibacterial activity and very low binding energies for glucosamine-6-phosphate synthetase (PDB Id: 1jxa).

4-AMINOQUINOLINE DERIVATIVES AS ANTIMALARIAL AGENTS: MOLECULAR DOCKING STUDI

Malaria is a parasite disease that can be lethal and is carried by mosquitoes. Scoring techniques that can evaluate intermolecular binding affinity or binding free energy are used to optimise and rank the molecular docking process. 15 variants of 4-aminoquinoline were docked in the binding pocket of the Oxidoreductase protein using the docking server's Ligand fit module (1ldg.pdb). The results demonstrated that the binding energies of compounds (N-(2-amino propyl)-7-chloro-quinoline-4-amine), (3-(3-(7-chloroquinolin-4-yl amino)propyl)-2-phenyl-1,3thiazinan-4-one), and (3-(3-(7-chloroquinolin -4-ylamino)propoyl)-2-(4-nitrophenyl)-1,3thiazinan-4-one). As a result, three of the fifteen compounds will effectively combat various plasmodium strains. Future attempts by other researchers to produce new antimalarial drugs may benefit from additional study to synthesise these powerful compounds and assess their performance.

In silico analysis of AhyI protein and AI-1 inhibition using N-cis-octadec-9z-enoyl-l-homoserine lactone inhibitor in Aeromonas hydrophila

AhyI is homologous to the protein LuxI and is conserved throughout bacterial species including Aeromonas hydrophila. A. hydrophila causes opportunistic infections in fish and other aquatic organisms. Furthermore, this pathogennot only poses a great risk for the aquaculture industry, but also for human public health. AhyI (expressing acylhomoserine lactone) is responsible for the biosynthesis of autoinducer-1 (AI-1), commonly referred to as a quorum sensing (QS) signaling molecule, which plays an essential role in bacterial communication. Studying protein structure is essential for understanding molecular mechanisms of pathogenicity in microbes. Here, we have deduced a predicted structure of AhyI protein and characterized its function using in silico methods to aid the development of new treatments for controlling A.hydrophila infections. In addition to modeling AhyI, an appropriate inhibitor molecule was identified via high throughput virtual screening (HTVS) using mcule drug-like databases.The AhyI-inhibitor N-cis-octadec-9Z-enoyl-l-Homoserine lactone was selected withthe best drug score. In order to understand the pocket sites (ligand binding sites) and their interaction with the selected inhibitor, docking (predicted protein binding complex) servers were used and the selected ligand was docked with the predicted AhyI protein model. Remarkably, N-cis-octadec-9Z-enoyl-l-Homoserine lactone established interfaces with the protein via16 residues (V24, R27, F28, R31, W34, V36, D45, M77, F82, T101, R102, L103, 104, V143, S145, and V168), which are involved with regulating mechanisms of inhibition. These proposed predictions suggest that this inhibitor molecule may be used as a novel drug candidate for the inhibition of auto-inducer-1 (AI-1) activity.The N-cis-octadec-9Z-enoyl-l-Homoserine lactone inhibitor molecule was studied on cultured bacteria to validate its potency against AI-1 production. At a concentration of 40 μM, optimal inhibition efficiency of AI-1 was observedin bacterial culture media.These results suggest that the inhibitor molecule N-cis-octadec-9Z-enoyl-l-Homoserine lactone is a competitive inhibitor of AI-1 biosynthesis.

Screening of new BACE‐1 inhibitors from marine animals: Molecular interaction and pharmacokinetic studies to find new drug prototypes

AbstractBackgroundOne cause of the Alzheimer's disease (AD) is the amyloid plaques accumulation, generated after an endoproteolytic cleavage of APP by secretases (WAKABAYASHI; STROOPER, 2008). Secretase inhibitors have been studied, but failed in clinical trials due to high toxicity and/or efficacy (HUNG; FU, 2017). So far, the main clinical treatment for AD is the administration of cholinesterase inhibitors that only increases the patient's survival in a few years (GAN et al., 2004). Molecules from natural products have been used as prototypes in the development of new drugs, and species from marine habitat have provided compounds of therapeutic interest, none of them applied to AD (MALVE, 2016). Thus, the objective of this work was to find new druggable β‐secretase (BACE1) inhibitors among molecules described from marine animals, aiming a new prototype for amyloid plaques decrease.MethodMolecules from marine animals were searched in scientific articles and prepared for docking, conducted by Swiss Dock server, to predict molecular interaction with BACE1 (PDB code 2VKM). Results were analyzed by UCSF Chimera, and molecules were selected if they were positioned in the enzyme active site, with distance lower than 3 Å and binding energy lower than ‐6 kcal/mol. Selected molecules were analyzed for their pharmacokinetics properties (PK) and druggability using the SwissADME server.ResultFrom 48 molecules, 3 were selected by molecular docking. Psammaplin A (PsA) is one of them, extracted from the poriferous Aplysin and known for its antibacterial and antitumor activities (SELEGHIM et al, 2007). It had favorable binding energy (−9.71 kcal/mol) and short distance between the ligand and the protein (1,923 and 2,615 Å2); however, its PK was not suitable for a drug. On the other hand, 1H‐Benzo[de][1,6]naphthyridine and Sebastianine A had lower binding energy as well (−6.76 and −6,98 kcal/mol, respectively) and favorable PK: logP ∼2.5, high gastrointestinal absorption, brain‐blood barrier permeant, low ability to inhibit liver enzymes and no violation of the Lipinski’s rules, characteristics to be druggable.ConclusionUsing molecular docking, 3 molecules were selected as potential inhibitors of BACE1, being two of them druggable and good prototypes for the treatment of AD.

DAMPAK KADMIUM DAN MERKURI TERHADAP METABOLISME KARBOHIDRAT: KAJIAN IN SILICO PADA ENZIM GLIKOGEN SINTASE DAN FOSFOFRUKTOKINASE

Cadmium (Cd) and Mercury (Hg) is a heavy metal with high cytotoxicity, implicated as causes of chronic inflammation, oxidative stress, obesity, hyperglycemia, and even diabetes. The long-term exposure of Cd and Hg can affect enzymes involved in carbohydrate metabolism, on the process of glycolysis and glycogenesis. by changing the structure and enzymatic activity of proteins which can cause toxic effects on enzymes involved therein including glycogen synthase (GS), which can cause glycogen content depletion and has potential to limit the glycolysis process in liver and muscles by decreasing the phosphofructokinase (PFK) enzyme activity. There are not many studies that explain the interactions between Cd and Hg on GS and PFK enzymes. For this reason, this research was carried out using in silico. The structure of the enzymes was obtained from the RCSB Protein Data Bank (http://www.rcsb.org) with the following code, GS (PDB ID: 1RZV) and PFK (PDB ID: 4WLO). The interactions between Cd and Hg with these enzymes were used by MIB: Metal Ion-Binding site prediction and docking server (http://bioinfo.cmu.edu.tw/MIB/). The interactions between Cd and amino acids of targeted protein were visualized on UCSF Chimera 1.14. The results showed that Hg interacted with amino acid residues at the active site of the glycogen synthase enzyme at the end of the C-terminal domain, namely at 3 cysteine ??residues Cys 295, cys 366, and cys 390. Meanwhile, Cd and Hg did not interact with amino acid residues. on the active site of the phosphofructokinase enzyme, but interacts with the protein structure of the enzyme.

Preliminary Phytochemical Screening and Bioactive Compounds of Swietenia macrophylla Seed Support T1DM and T2DM

The purpose of this study was to investigate the antidiabetic effect of phytocompounds from Swietenia macrophylla seed using preliminary phytochemical screening, invitro antioxidant activity and molecular docking studies. The powdered seed extract of Swietenia macrophylla was to investigate the phytochemical screening exhibited the presence of alkaloid, phenols, tannins, flavonoids, terpenoids, steroids, carbohydrates, amino acids and proteins as major active constituents. The antioxidant activity of Swietenia macrophylla seed was evaluated by DPPH free radical scavenging assay. Rutin was used as a reference compound. The Swietenia macrophylla seed exhibited 56.0471% of free radical scavenging activity as compared with rutin. The molecular docking studies performed by using molecular docking server online respectively in which the antidiabetic target namely glutamine:fructose-6-phosphate amidotransferase (GFAT) (PDB id: 2ZJ3) have a potential interaction with swietenine, swietenolide, β-sitosterol, and fucosterol. In this study, the protein glutamine:fructose-6-phosphate amidotransferase (GFAT) was used from its structure perspectives. Its primary and secondary structures were evaluated using online tools. Its role in antidiabetic was assessed by molecular docking the compounds present in the seed extract of Swietenia macrophylla assayed by GC-MS analysis. This in-silico study demonstrates the interactions of active components of Swietenia macrophylla against Type I and Type II diabetes.

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.

Exploring the interaction of quercetin-3-O-sophoroside with SARS-CoV-2 main proteins by theoretical studies: A probable prelude to control some variants of coronavirus including Delta

The aim of this study was to investigate the mechanism of interaction between quercetin-3-O-sophoroside and different SARS-CoV-2’s proteins which can bring some useful details about the control of different variants of coronavirus including the recent case, Delta. The chemical structure of the quercetin-3-O-sophoroside was first optimized. Docking studies were performed by CoV disease-2019 (COVID-19) Docking Server. Afterwards, the molecular dynamic study was done using High Throughput Molecular Dynamics (HTMD) tool. The results showed a remarkable stability of the quercetin-3-O-sophoroside based on the calculated parameters. Docking outcomes revealed that the highest affinity of quercetin-3-O-sophoroside was related to the RdRp with RNA. Molecular dynamic studies showed that the target E protein tends to be destabilized in the presence of quercetin-3-O-sophoroside. Based on these results, quercetin-3-O-sophoroside can show promising inhibitory effects on the binding site of the different receptors and may be considered as effective inhibitor of the entry and proliferation of the SARS-CoV-2 and its different variants. Finally, it should be noted, although this paper does not directly deal with the exploring the interaction of main proteins of SARS-CoV-2 Delta variant with quercetin-3-O-sophoroside, at the time of writing, no direct theoretical investigation was reported on the interaction of ligands with the main proteins of Delta variant. Therefore, the present data may provide useful information for designing some theoretical studies in the future for studying the control of SARS-CoV-2 variants due to possible structural similarity between proteins of different variants.

Inhibitory activity of Urena lobata leaf extract on alpha-amylase and alpha-glucosidase: in vitro and in silico approach.

In food ingestion, alpha-glucosidase (α-glucosidase) and alpha-amylase (α-amylase) are enzymes that are responsible to convert a carbohydrate into glucose. Inhibition of both enzyme activities can prolong absorption of glucose in intestine and reduce post-prandial increase of blood glucose concentration, thus, it is beneficial for type-2 diabetes treatment. Traditionally, Urena lobata (U.lobata) has been used to manage diabetes, but the scientific proof of this claim remains scarce. Therefore, the objective of thisstudy to examine the anti-diabetic potential of U.lobata leaf extract through inhibition of α-amylase and α-glucosidase. U.lobata leaf extract was obtained through extraction process using ethanol and the chemical compounds in the extract were analyzed by liquid chromatography-mass spectra (LC-MS). The inhibitory activity of U.lobata on α-glucosidase and α-amylase was evaluated by in silico using docking server, whereas in vitro enzymatic assays were using para-nitrophenyl-α-d-glucopyranoside (α-NPG) and starch as substrates. The data were presented as mean±SD and the IC50 value was calculated using SPSS. U.lobata leaf extract showed inhibitory activity on α-glucosidase and α-amylase with the IC50 value was 43.73 and 83.73μg/mL, respectively, meanwhile, acarbose as standard has IC50 value at 1.14 and 0.08μg/mL. Molecular docking study indicated β-sitosterol and stigmasterol from U.lobata extract have a huge inhibitory activity both on α-amylase and α-glucosidase based on inhibition constant (Ki) value. Ethanolic extract of U.lobata showed inhibition activity on α-glucosidase stronger than on α-amylase as antidiabetic.

In Silico Investigation on the Interaction of Chiral Phytochemicals from Opuntia ficus-indica with SARS-CoV-2 Mpro

Opuntia ficus-indica is a cactaceous plant native to America but, nowadays, widely found worldwide, having been the most common domesticated species of cactus grown as a crop plant in semiarid and arid parts of the globe, including several Mediterranean basin countries. Opuntia ficus-indica can be regarded as a medicinal plant, being source of numerous bioactive phytochemicals such as vitamins, polyphenols, and amino acids. The urgent need for therapeutic treatments for the COronaVIrus Disease 19 (COVID-19), caused by the Severe Acute Respiratory Syndrome (SARS)-Coronavirus (CoV)-2, justifies the great attention currently being paid not only to repurposed antiviral drugs, but also to natural products and herbal medications. In this context, the anti-COVID-19 utility of Opuntia ficus-indica as source of potential antiviral drugs was investigated in this work on the basis of the activity of some of its phytochemical constituents. The antiviral potential was evaluated in silico in docking experiments with Mpro, i.e., the main protease of SARS-CoV-2, that is one of the most investigated protein targets of therapeutic strategies for COVID-19. By using two web-based molecular docking programs (1-Click Mcule and COVID-19 Docking Server), we found, for several flavonols and flavonol glucosides isolated from Opuntia ficus-indica, good binding affinities for Mpro, and in particular, binding energies lower than −7.0 kcal/mol were predicted for astragalin, isorhamnetin, isorhamnetin 3-O-glucoside, 3-O-caffeoyl quinic acid, and quercetin 5,4′-dimethyl ether. Among these compounds, the chiral compound astragalin showed in our in silico studies the highest affinity for Mpro (−8.7 kcal/mol) and also a low toxicity profile, emerging, thus, as an interesting protease inhibitor candidate for anti-COVID-19 strategies.

Molecular docking study and mapping the binding site of some antiviral nanobodies against receptor binding domain (RBD) of SARS-COV 2

Neutralization ability of some antiviral nanobodies was computed against the receptor binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-COV 2). CoDockPP Server and COVID-19 Docking Server respectively was applied for a protein-protein molecular docking. The affinity of candidate nonobodies was investigated for blocking of RBD against the human angiotensin coverting enzyme 2 (ACE2). The neutralization ability of nonobodies was compared with natural nanobodies of Ty1, H11-H4, EY6A, H11-D4 and synthetic construct of Sb23, ybody MR17, sybody MR17-K99Y, and SR4 that experimentally was involved against the RBD of SARS-COV 2. It was seen, the 15 reported VHH was able for blocking with an estimated binding energy greater than -235.55 (kcal/mol) for Ty1 with the lowest affinity to the RBD. VHH 7A, VHH PVSP29F, Cameld VHH 9, VHH PVSS8A, VHH 12B, VHH 59H10, VHH PVSP6A, VHH 10E, VHH 17B and VHH 59H10 respectively was proposed for neutralization of RBD while the two last VHH are more confidence due to the greater values of affinity against -342.56 (kcal/mol) for SR4. The energy maps of ACE2, VHH 17B and VHH 59H10 was identified that hydrogen donor, steric, hydrogen acceptor and electrostatic interactions respectively were significant for blocking RBD of SARS-COV 2. This study conform structural insight for neutralization of RBD spike glycoprotein of SARS-COV 2 by nanobodies and suggest VHH that may serve as useful therapeutics during the pandemic.

InterEvDock3: a combined template-based and free docking server with increased performance through explicit modeling of complex homologs and integration of covariation-based contact maps.

The InterEvDock3 protein docking server exploits the constraints of evolution by multiple means to generate structural models of protein assemblies. The server takes as input either several sequences or 3D structures of proteins known to interact. It returns a set of 10 consensus candidate complexes, together with interface predictions to guide further experimental validation interactively. Three key novelties were implemented in InterEvDock3 to help obtain more reliable models: users can (i) generate template-based structural models of assemblies using close and remote homologs of known 3D structure, detected through an automated search protocol, (ii) select the assembly models most consistent with contact maps from external methods that implement covariation-based contact prediction with or without deep learning and (iii) exploit a novel coevolution-based scoring scheme at atomic level, which leads to significantly higher free docking success rates. The performance of the server was validated on two large free docking benchmark databases, containing respectively 230 unbound targets (Weng dataset) and 812 models of unbound targets (PPI4DOCK dataset). Its effectiveness has also been proven on a number of challenging examples. The InterEvDock3 web interface is available at http://bioserv.rpbs.univ-paris-diderot.fr/services/InterEvDock3/.

Predicting Multi-Epitope Peptide Cancer Vaccine from Novel TAA Topo48

Cancer is one of the most lethal diseases. Recently, cancer immunotherapy has a tremendous achievement in cancer treatment. A certain number of cancer based epitope vaccines with different moiety have been discovered. In japan, several clinical tests of cancer based epitope vaccine derived from tumor associated antigens (TAAs) are now ongoing or have recently been completed. a novel of TAAs potentially as cancer vaccine have been retrieved from a fragment weighed 48kDa derived from human DNA-topoisomerase 1 (TOP1) called Topo48. Therefore, it is still critical to discover a derived Topo48 epitope based cancer vaccine. Immuno-informatics considered as a methods noted to have better accuracy to design promising vaccine candidates. Here, continuous and discontinuous B-cell epitopes following with CTL epitopes and their docking interaction to major histocompatibility complex (MHC) class I Human Leukocyte Antigens (HLA)- A0201 were predicted. Kolaskar-Tongaonkar’s, Emini’s, Karpus-Schulz’s, and Parker’s methods were used to predict continuous B-cell epitopes while ElliPro was used for prediction of discontinued B-cell epitopes. Those considered methods marked to have better accuracy to design promising vaccine candidates. Similarly, CTL epitopes was also predicted by using NetCTL server and the best candidates were further investigated their binding affinity by mean of PEP-FOLD3, PatchDock rigid-body docking server, and FireDock server. Total 27 continuous epitopes and 7 discontinuous B-cell epitopes were predicted. In the other hand, 9 peptides were predicted as CTL epitopes. Whereas, three predicted CTL epitope in range 263MLDHEYTTK27, 755AIDMADEDY763, 715ALGTSKLNY724) exhibited good interactions to HLA-A0201. Moreover, we also found residues His266, Thr270, Ala755, Tyr723, Thr718, Ser719, Lys720 from Topo48 and residues Thr163, Asp757, His70, Glu63 from HLA- A0201 were indicated to be antigenic. Ultimately, our proposed continuous/discontinuous B-cell epitopes, and also CTL epitopes can be potential vaccines for cancer immunotherapy.

An Analysis of Inhibition of the Severe Acute Respiratory Syndrome Coronavirus 2 RNA-dependent Rna Polymerase By Zinc Ion: an in silico Approach

Background: Coronavirus disease 2019 is caused by exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was reported that Zn2+ is an inhibitor of severe acute respiratory syndrome coronavirus (SARS-CoV). We hypothesize that the same applies to the newly discovered SARS-CoV-2. Material & methods: We compared the structure of RNA-dependent RNA polymerase between SARS-CoV and SARS-CoV-2. The RdRp’s binding to Zn2+ was studied by metal ion-binding site prediction and docking server. Results: Several regions containing key residues were detected. The functional aspartic acid residues RdRp, 618D, 760D and 761D were among the predicted Zn2+-binding residues. Conclusion: The most probable mechanism of inhibition of RdRp by Zn2+ is binding to the active aspartic acid triad while other binding sites can further destabilize the enzyme or interfere with the fidelity-check mechanism.

In silico investigation of the potential interaction between two entomological peptides and human androgen receptor

Objective: We aim to evaluate the potential interaction of two insect hemolymph peptides, MDF3 and MDF4, with the human androgen receptor, on the premise that the proliferative effects of the two peptides are (at least in part) a consequence of AR binding. Methods: We employed a bioinformatic approach for the prediction of protein-peptide interaction and peptide aggregation, using various in silico on-line tools such as docking servers, aggregation prediction servers and visualization and analysis software in order to evaluate our results. Results: Our evaluation indicates that MDF3 and MDF4 interact with the androgen human androgen receptor by binding to a helix shown to be involved the receptor dimerization. Out of the two peptides, MDF3 appears to form a more extensive bond network with the receptor. Conclusion: Our analysis indicates that MDF 3 and 4 may be able to activate the human androgen receptor and warrant further investigation of the potential effect on receptor function. MDF3 appears to be the most promising out of the two peptides and its interaction should be further evaluated by both computational and experimental methods.

A molecular docking study of SARS-CoV-2 main protease against phytochemicals of Boerhavia diffusa Linn. for novel COVID-19 drug discovery.

SARS-CoV-2, the causative virus of the Corona virus disease that was first recorded in 2019 (COVID-19), has already affected over 110 million people across the world with no clear targeted drug therapy that can be efficiently administered to the wide spread victims. This study tries to discover a novel potential inhibitor to the main protease of the virus, by computer aided drug discovery where various major active phytochemicals of the plant Boerhavia diffusa Linn. namely 2-3-4 beta-Ecdysone, Bioquercetin, Biorobin, Boeravinone J, Boerhavisterol, kaempferol, Liriodendrin, quercetin and trans-caftaric acid were docked to SAR-CoV-2 Main Protease using Molecular docking server. The ligands that showed the least binding energy were Biorobin with − 8.17 kcal/mol, Bioquercetin with − 7.97 kcal/mol and Boerhavisterol with − 6.77 kcal/mol. These binding energies were found to be favorable for an efficient docking and resultant inhibition of the viral main protease. The graphical illustrations and visualizations of the docking were obtained along with inhibition constant, intermolecular energy (total and degenerate), interaction surfaces and HB Plot for all the successfully docked conditions of all the 9 ligands mentioned. Additionally the druglikeness of the top 3 hits namely Bioquercetin, Biorobin and Boeravisterol were tested by ADME studies and Boeravisterol was found to be a suitable candidate obeying the Lipinsky’s rule. Since the main protease of SARS has been reported to possess structural similarity with the main protease of MERS, comparative docking of these ligands were also carried out on the MERS Mpro, however the binding energies for this target was found to be unfavorable for spontaneous binding. From these results, it was concluded that Boerhavia diffusa possess potential therapeutic properties against COVID-19.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13337-021-00683-6.