scholarly journals Conformational Epitope Prediction of Birch Betv 1 and Hazel Cor A1 Towards B-Cells

2021 ◽  
pp. 146-159
Author(s):  
Namratha Boddakayala ◽  
Sreedhar Bodiga ◽  
Vijaya Lakshmi Bodiga ◽  
Pavan Kumar Tummala ◽  
Srikanth Vemuru ◽  
...  
Keyword(s):  
Epitope Prediction ◽  
Conformational Epitope ◽  
Docking Studies ◽  
Binding Energies ◽  
Antigenic Determinants ◽  
World Population ◽  
White Birch ◽  
Ige Antibody ◽  
Bet V1 ◽  
Antigen Antibody

Background: White birch and hazel allergens, namely Bet v1 and Cor a1 are known allergens, but their allergen specificity is not yet characterized. Objective: To map the antigenic determinants responsible for IgE binding utilizing in silico modelling and docking of the peptides against IgE antibody. Methods: The antigen sequences were cut into peptides are docked against the IgE antibody and those with the highest docking scores are further studied for the bond interactions. The overlapping sequences of the high score peptides are observed in the whole antigen model to predict their position. The residues at bond interactions also been reported for these overlapping peptide sequences. Results: The validation is done by antigen-antibody docking studies to confirm the predicted epitope. 25% of the world population suffers from allergic rhinitis and 15% of them develop asthma. Conclusion: Negative binding energies of the studied pollen allergens with IgE confirm their allergenicity. Based on the results of overlapping peptides PF 3,4 and PF 16,17 to play a key role in the allergenic response of white birch and Common hazel.

Localization of Intracellular Antigens in thin Sections with Ferritin Labeled Antibody

1970 ◽  
Vol 28 ◽  
pp. 174-175
Author(s):  
M.S. Shahrabadi ◽  
T. Yamamoto
Keyword(s):  
Bovine Serum Albumin ◽  
Bovine Serum ◽  
Antigenic Determinants ◽  
Conjugate Prior ◽  
Thin Sections ◽  
Specific Attachment ◽  
Intracellular Antigen ◽  
Antigen Antibody ◽  
Ideal Method ◽  
The Ideal

The technique of labeling of macromolecules with ferritin conjugated antibody has been successfully used for extracellular antigen by means of staining the specimen with conjugate prior to fixation and embedding. However, the ideal method to determine the location of intracellular antigen would be to do the antigen-antibody reaction in thin sections. This technique contains inherent problems such as the destruction of antigenic determinants during fixation or embedding and the non-specific attachment of conjugate to the embedding media. Certain embedding media such as polyampholytes (2) or cross-linked bovine serum albumin (3) have been introduced to overcome some of these problems.

In silico Discovery of Resveratrol Analogues as Potential Agents in Treatment of Metabolic Disorders

2019 ◽  
Vol 25 (35) ◽  
pp. 3776-3783
Author(s):  
Nebojša Pavlović ◽  
Maja Đanić ◽  
Bojan Stanimirov ◽  
Svetlana Goločorbin-Kon ◽  
Karmen Stankov ◽  
...  
Keyword(s):  
In Silico ◽  
Metabolic Disorders ◽  
Partial Agonist ◽  
Aqueous Solubility ◽  
Structural Similarity ◽  
Data Bank ◽  
Docking Studies ◽  
Binding Energies ◽  
Molegro Virtual Docker ◽  
Ppar Γ

Background: Resveratrol was demonstrated to act as partial agonist of PPAR-γ receptor, which opens up the possibility for its use in the treatment of metabolic disorders. Considering the poor bioavailability of resveratrol, particularly due to its low aqueous solubility, we aimed to identify analogues of resveratrol with improved pharmacokinetic properties and higher binding affinities towards PPAR-γ. Methods: 3D structures of resveratrol and its analogues were retrieved from ZINC database, while PPAR-γ structure was obtained from Protein Data Bank. Docking studies were performed using Molegro Virtual Docker software. Molecular descriptors relevant to pharmacokinetics were calculated from ligand structures using VolSurf+ software. Results: Using structural similarity search method, 56 analogues of resveratrol were identified and subjected to docking analyses. Binding energies were ranged from -136.69 to -90.89 kcal/mol, with 16 analogues having higher affinities towards PPAR-γ in comparison to resveratrol. From the calculated values of SOLY descriptor, 23 studied compounds were shown to be more soluble in water than resveratrol. However, only two tetrahydroxy stilbene derivatives, piceatannol and oxyresveratrol, had both better solubility and affinity towards PPAR-γ. These compounds also had more favorable ADME profile, since they were shown to be more metabolically stable and wider distributed in body than resveratrol. Conclusion: Piceatannol and oxyresveratrol should be considered as potential lead compounds for further drug development. Although experimental validation of obtained in silico results is required, this work can be considered as a step toward the discovery of new natural and safe drugs in treatment of metabolic disorders.

Immunochemical Studies on Antithrombin III

1979 ◽  
Author(s):  
E.J. McKay
Keyword(s):  
Antithrombin Iii ◽  
The Other ◽  
Antigenic Determinants ◽  
Immunochemical Analysis ◽  
Paradoxical Effect ◽  
Test Protocol ◽  
Agar Gel ◽  
High Affinity ◽  
Time Required ◽  
Antigen Antibody

Depressed Antithrombin III (AT) levels Increase thrombic tendency in man, therefore value in assaying this protein has been established. Immunochemical analysis of AT in clinical disease has however proved controversial, consequently systematic studies were undertaken to rationalize the requirements necessary to optimise these methods in particular electro-Immunoassay. The known binding affinity of AT for heparin has been exploited to differentiate high affinity AT from its inhibitor - protease complexes and has resulted in reports stating that heparin added to the agar gel prior to electrophoresis significantly reduces the time required for completion of antigen/antibody complexes. Our studies however have demonstrated that the antibody required for quantitative analysis must be capable of not only reacting with “native” antigenic determinants of AT but also with “neo” antigens that are exposed when inhibitor-protease complexes are formed. Heparin should not be used in the test protocol, for it has a paradoxical effect on Immunopreclpltation in gels, masking some antigenic determinants of unbound - high affinity AT on one hand, and appear to disrupt the Immunoprecipitin “rocket” formed with the inhibitor-protease complexes during electrophoresis on the other.

Demonstration of the Exposure of New Antigenic Determinants Following Antigen–antibody Combination

Nature ◽  
1965 ◽  
Vol 205 (4976) ◽  
pp. 1079-1081 ◽  
Author(s):  
C. S. HENNEY ◽  
D. R. STANWORTH ◽  
P. G. H. GELL
Keyword(s):  
Antigenic Determinants ◽  
Antigen Antibody

scholarly journals Advances in the Treatment of Explicit Water Molecules in Docking and Binding Free Energy Calculations

2020 ◽  
Vol 26 (42) ◽  
pp. 7598-7622 ◽  
Author(s):  
Xiao Hu ◽  
Irene Maffucci ◽  
Alessandro Contini
Keyword(s):  
Drug Discovery ◽  
Binding Free Energy ◽  
Docking Studies ◽  
Free Energy Calculations ◽  
Binding Energies ◽  
New Drugs ◽  
Water Molecules ◽  
Open Questions ◽  
Dynamics Simulations ◽  
Computational Drug Discovery

Background: The inclusion of direct effects mediated by water during the ligandreceptor recognition is a hot-topic of modern computational chemistry applied to drug discovery and development. Docking or virtual screening with explicit hydration is still debatable, despite the successful cases that have been presented in the last years. Indeed, how to select the water molecules that will be included in the docking process or how the included waters should be treated remain open questions. Objective: In this review, we will discuss some of the most recent methods that can be used in computational drug discovery and drug development when the effect of a single water, or of a small network of interacting waters, needs to be explicitly considered. Results: Here, we analyse the software to aid the selection, or to predict the position, of water molecules that are going to be explicitly considered in later docking studies. We also present software and protocols able to efficiently treat flexible water molecules during docking, including examples of applications. Finally, we discuss methods based on molecular dynamics simulations that can be used to integrate docking studies or to reliably and efficiently compute binding energies of ligands in presence of interfacial or bridging water molecules. Conclusions: Software applications aiding the design of new drugs that exploit water molecules, either as displaceable residues or as bridges to the receptor, are constantly being developed. Although further validation is needed, workflows that explicitly consider water will probably become a standard for computational drug discovery soon.

scholarly journals Studies on the antigenic determinants in the self-association of IgG rheumatoid factor

1981 ◽  
Vol 154 (1) ◽  
pp. 112-125 ◽  
Author(s):  
FA Nardella ◽  
DC Teller ◽  
M Mannik
Keyword(s):  
Sedimentation Equilibrium ◽  
Antigenic Determinants ◽  
Fab Fragment ◽  
Fab Fragments ◽  
Polymer Formation ◽  
Igg Rheumatoid Factor ◽  
Normal Human ◽  
Self Association ◽  
Equilibrium Ultracentrifugation ◽  
Antigen Antibody

The number, location, and other characteristics of the antigenic determinants for self-association of IgG-rheumatoid factors (IgG-RF) were examined using the IgG-RF isolated from the plasma of one patient as a model system. Affinity chromatography was employed for isolation of the IgG-RF. Sedimentation equilibrium ultracentrifugation was used to study the various interactions. The antigenic valence of IgG-RF Fc, normal human Fc, and rabbit Fc fragments was two for the interaction with Fab fragments from IgG-RF, as might be expected from the molecular symmetry of IgG. The antigenic valence of intact normal IgG, however, was only one, indicating that when one of the available antigenic determinants interacted with the Fab fragment of IgG-RF, the other determinant becomes sterically inaccessible. Reduction and alkylation, known to increase the flexibility of the hinge region, did not alter the antigenic valence of IgG for Fab fragments of IgG-RF. The antigenic valence of IgG-RF in self-association could not be experimentally determined but must be two to permit the observed concentration-dependent further polymer formation of IgG-RF dimers. Unique antigenic determinants on the Fc fragments of IgG-RF were sought and not found, thus reaffirming the formation of two antigen-antibody bonds as the basis for dimerization of IgG-RF molecules. The pFc' and Fc' fragments, representing Cγ3 domains of IgG, failed to show significant interaction with Fab fragments of IgG-RF, indicating that the antigenic determinants were not expressed by the Cγ3 regions but are located either on Cγ2 region or require intact Cγ2 and Cγ3 regions for expression. These conclusions were corroborated by the antigenic valence of one for the Fc(i) fragment, a new papain-generated intermediate fragment of Fc, composed of two intact Cγ3 domains and one intact Cγ2 domain. Normal IgG, because of its valence of one for interaction with IgG-RF, would effectively terminate further polymerization of IgG-RF dimers. This may well in part explain the finding of smaller IgG-RF complexes in the serum than in synovial fluid of patients with rheumatoid arthritis.

scholarly journals CEP: a conformational epitope prediction server

2005 ◽  
Vol 33 (Web Server) ◽  
pp. W168-W171 ◽  
Author(s):  
U. Kulkarni-Kale ◽  
S. Bhosle ◽  
A. S. Kolaskar
Keyword(s):  
Epitope Prediction ◽  
Conformational Epitope ◽  
Prediction Server

Pyrazole Schiff Base Hybrids as Anti-Malarial Agents: Synthesis, In Vitro Screening and Computational Study

2018 ◽  
Vol 21 (3) ◽  
pp. 194-203 ◽  
Author(s):  
Shilpy Aggarwal ◽  
Deepika Paliwal ◽  
Dhirender Kaushik ◽  
Girish Kumar Gupta ◽  
Ajay Kumar
Keyword(s):  
Schiff Base ◽  
Antimalarial Activity ◽  
Computational Study ◽  
Docking Study ◽  
Docking Studies ◽  
Binding Energies ◽  
Study Results ◽  
Wide Range ◽  
Parasite Plasmodium Falciparum

Background: Malaria is one of the most vital infectious diseases caused by protozoan parasites of the Plasmodium genus. As P. falciparum, the cause of most of the severe cases of malaria, is increasingly resistant to available drugs such as amodioquine, chloroquine, artemisinin, and antifolates, there is an urgent need to identify new targets for chemotherapy. Objective: This study screened novel pyrazole derivatives carrying iminium & benzothiazole group for antimalarial potential against P. falciparum chloroquine sensitive (3D7) strain. Materials & Methods: Several pyrazole schiff base hybrids with a wide range of substitution have been synthesized via condensation of substituted aniline with substituted 4-formylpyrazole and evaluated for their in vitro antimalarial activity against asexual blood stages of human malaria parasite, Plasmodium falciparum. The interaction of these conjugate hybrids was also investigated by molecular docking studies in the binding site of P. falciparum cystein protease falcipain-2. The pharmacokinetic properties were also studied using ADME prediction. Results: Among all compounds, 6bf and 6bd were found to be potential molecules with EC50 1.95µg/ml and 1.98µg/ml respectively. Docking study results reveal that the pyrazole schiff base derivatives occupy the PfFP binding sites and they show good interactions with significant values of binding energies. Conclusion: We provide evidence which implicates pyrazole Schiff base hybrids as potential prototypes for the development of antimalarial agents.

scholarly journals Homology Modelling and Molecular Docking Studies of Selected Substituted Benzo[d]imidazol-1-yl)methyl)benzimidamide Scaffolds on Plasmodium falciparum Adenylosuccinate Lyase Receptor

2019 ◽  
Vol 13 ◽  
pp. 117793221986553 ◽  
Author(s):  
Gbolahan O Oduselu ◽  
Olayinka O Ajani ◽  
Yvonne U Ajamma ◽  
Benedikt Brors ◽  
Ezekiel Adebiyi
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Docking ◽  
In Silico ◽  
Homology Modelling ◽  
3D Structure ◽  
Docking Studies ◽  
Binding Energies ◽  
Benzimidazole Derivatives ◽  
Adenylosuccinate Lyase ◽  
In Silico Admet

Plasmodium falciparum adenylosuccinate lyase ( PfADSL) is an important enzyme in purine metabolism. Although several benzimidazole derivatives have been commercially developed into drugs, the template design as inhibitor against PfADSL has not been fully explored. This study aims to model the 3-dimensional (3D) structure of PfADSL, design and predict in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) of 8 substituted benzo[ d]imidazol-1-yl)methyl)benzimidamide compounds as well as predict the potential interaction modes and binding affinities of the designed ligands with the modelled PfADSL. PfADSL 3D structure was modelled using SWISS-MODEL, whereas the compounds were designed using ChemDraw Professional. ADMET predictions were done using OSIRIS Property Explorer and Swiss ADME, whereas molecular docking was done with AutoDock Tools. All designed compounds exhibited good in silico ADMET properties, hence can be considered safe for drug development. Binding energies ranged from −6.85 to −8.75 kcal/mol. Thus, they could be further synthesised and developed into active commercial antimalarial drugs.

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