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Journal ArticleDOI

Designing a Multi-Epitope Vaccine against Chlamydia trachomatis by Employing Integrated Core Proteomics, Immuno-Informatics and In Silico Approaches

TL;DR: In this article, the authors used core proteomics, immuno-informatics, and subtractive proteomics approaches to identify the best antigenic candidates for the development of a multi-epitope-based vaccine (MEBV).
Abstract: Chlamydia trachomatis, a Gram-negative bacterium that infects the rectum, urethra, congenital sites, and columnar epithelium of the cervix. It is a major cause of preventable blindness, ectopic pregnancy, and bacterial sexually transmitted infections worldwide. There is currently no licensed multi-epitope vaccination available for this pathogen. This study used core proteomics, immuno-informatics, and subtractive proteomics approaches to identify the best antigenic candidates for the development of a multi-epitope-based vaccine (MEBV). These approaches resulted in six vaccine candidates: Type III secretion system translocon subunit CopD2, SctW family type III secretion system gatekeeper subunit CopN, SycD/LcrH family type III secretion system chaperone Scc2, CT847 family type III secretion system effector, hypothetical protein CTDEC_0668, and CHLPN 76kDa-like protein. A variety of immuno-informatics tools were used to predict B and T cell epitopes from vaccine candidate proteins. An in silico vaccine was developed using carefully selected epitopes (11 CTL, 2 HTL & 10 LBL) and then docked with the MHC molecules (MHC I & MHC II) and human TLR4. The vaccine was coupled with Cholera toxin subunit B (CTB) adjuvant to boost the immune response. Molecular dynamics (MD) simulations, molecular docking, and MMGBSA analysis were carried out to analyze the molecular interactions and binding affinity of MEBV with TLR4 and MHC molecules. To achieve the highest level of vaccine protein expression, the MEBV was cloned and reverse-translated in Escherichia coli. The highest level of expression was achieved, and a CAI score of 0.97 was reported. Further experimental validation of the MEBV is required to prove its efficacy. The vaccine developed will be useful in preventing infections caused by C. trachomatis.
Citations
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Journal ArticleDOI
TL;DR: Four highly active constituents, namely, abrusin, abrisapogenol J, precatorine, and cycloartenol, help in improving the body’s sensitivity to insulin and regulate the expression of AKT1, MAPK3, TNFalpha, and MAPK1, which may act as potential therapeutic targets of T2DM.
Abstract: Type 2 diabetes mellitus (T2DM) is a notable health care load that imposes a serious impact on the quality of life of patients. The small amount of reported data and multiple spectra of pathophysiological mechanisms of T2DM make it a challenging task and serious economic burden in health care management. Abrus precatorius L. is a slender, perennial, deciduous, and woody twining plant used in various regions of Asia to treat a variety of ailments, including diabetes mellitus. Various in vitro studies revealed the therapeutic significance of A. precatorius against diabetes. However, the exact molecular mechanism remains unclarified. In the present study, a network pharmacology technique was employed to uncover the active ingredients, their potential targets, and signaling pathways in A. precatorius for the treatment of T2DM. In the framework of this study, we explored the active ingredient–target–pathway network and figured out that abrectorin, abrusin, abrisapogenol J, sophoradiol, cholanoic acid, precatorine, and cycloartenol decisively contributed to the development of T2DM by affecting AKT1, MAPK3, TNFalpha, and MAPK1 genes. Later, molecular docking was employed to validate the successful activity of the active compounds against potential targets. Lastly, we conclude that four highly active constituents, namely, abrusin, abrisapogenol J, precatorine, and cycloartenol, help in improving the body’s sensitivity to insulin and regulate the expression of AKT1, MAPK3, TNFalpha, and MAPK1, which may act as potential therapeutic targets of T2DM. Integrated network pharmacology and docking analysis revealed that A. precatorius exerted a promising preventive effect on T2DM by acting on diabetes-associated signaling pathways. This provides a basis to understand the mechanism of the anti-diabetes activity of A. precatorius.

21 citations

Journal ArticleDOI
TL;DR: Wang et al. as discussed by the authors used reverse vaccinology-based immunoinformatics approach on four target proteins to better understand thermodynamic stability, binding affinities, and interaction of vaccine.

10 citations

Journal ArticleDOI
TL;DR: In this paper , a multi-epitope vaccine against EBOV was designed using immunoinformatics tools, and the results of codon optimization and in silico cloning revealed that the proposed vaccine was highly expressed in E. coli.
Abstract: Ebola virus (EBOV) is a dangerous zoonotic infectious disease. To date, more than 25 EBOV outbreaks have been documented, the majority of which have occurred in Central Africa. The rVSVG-ZEBOV-GP vaccine (ERVEBO), a live attenuated vaccine, has been approved by the US Food and Drug Administration (FDA) to combat EBOV. Because of the several drawbacks of live attenuated vaccines, multi-epitope vaccines probably appear to be safer than live attenuated vaccines. In this work, we employed immunoinformatics tools to design a multi-epitope vaccine against EBOV. We collected sequences of VP35, VP24, VP30, VP40, GP, and NP proteins from the NCBI database. T-cell and linear B-cell epitopes from target proteins were identified and tested for antigenicity, toxicity, allergenicity, and conservancy. The selected epitopes were then linked together in the vaccine's primary structure using appropriate linkers, and the 50S ribosomal L7/L12 (Locus RL7 MYCTU) sequence was added as an adjuvant to the vaccine construct's N-terminal. The physicochemical, antigenicity, and allergenicity parameters of the vaccine were all found to be satisfactory. The 3D model of the vaccine was predicted, refined, and validated. The vaccine construct had a stable and strong interaction with toll-like receptor 4 (TLR4) based on molecular docking and molecular dynamic simulation (MD) analysis. The results of codon optimization and in silico cloning revealed that the proposed vaccine was highly expressed in Escherichia coli (E. coli). The findings of this study are promising; however, experimental validations should be carried out to confirm these findings.

8 citations

Journal ArticleDOI
22 Nov 2021-Vaccine
TL;DR: Wang et al. as mentioned in this paper combined immunological approaches with molecular docking approaches for three highly antigenic proteins to design vaccines against Klebsiella aerogenes, and the synthesis of the B-cell, T-cell (CTL and HTL) and IFNγ epitopes of the targeted proteins was performed and most conserved epitopes were chosen for future research studies.

7 citations

Journal ArticleDOI
TL;DR: The need for further fundamental studies in this area in order to eradicate this infection is supported and the implementation of a Chlamydia Screening Program in Portugal is suggested.
Abstract: Chlamydia is one of the most common sexually transmitted bacterial infections (STIs) worldwide. It is caused by Chlamydia trachomatis (CT), which is an obligate intracellular bacterium. In some cases, it can occur in coinfection with other parasites, increasing the pathologic potential of the infection. The treatment is based on antibiotic prescription; notwithstanding, the infection is mostly asymptomatic, which increases the risk of transmission. Therefore, some countries have implemented Chlamydia Screening Programs in order to detect undiagnosed infections. However, in Portugal, there is no CT screening plan within the National Health Service. There is no awareness in the general healthcare about the true magnitude of this issue because most of the methods used are not Nucleic Acid Amplification Technology-based and, therefore, lack sensitivity, resulting in underreporting infection cases. CT infections are also associated with possible long-term severe injuries. In detail, persistent infection triggers an inflammatory milieu and can be related to severe sequels, such as infertility. This infection could also trigger gynecologic tumors in women, evidencing the urgent need for cost-effective screening programs worldwide in order to detect and treat these individuals adequately. In this review, we have focused on the success of an implemented screening program that has been reported in the literature, the efforts made concerning the vaccine discovery, and what is known regarding CT infection. This review supports the need for further fundamental studies in this area in order to eradicate this infection and we also suggest the implementation of a Chlamydia Screening Program in Portugal.

5 citations

References
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Journal ArticleDOI
TL;DR: A new membrane protein topology prediction method, TMHMM, based on a hidden Markov model is described and validated, and it is discovered that proteins with N(in)-C(in) topologies are strongly preferred in all examined organisms, except Caenorhabditis elegans, where the large number of 7TM receptors increases the counts for N(out)-C-in topologies.

11,453 citations

Journal ArticleDOI
TL;DR: The dbSNP database is a general catalog of genome variation to address the large-scale sampling designs required by association studies, gene mapping and evolutionary biology, and is integrated with other sources of information at NCBI such as GenBank, PubMed, LocusLink and the Human Genome Project data.
Abstract: In response to a need for a general catalog of genome variation to address the large-scale sampling designs required by association studies, gene mapping and evolutionary biology, the National Center for Biotechnology Information (NCBI) has established the dbSNP database [S.T.Sherry, M.Ward and K.Sirotkin (1999) Genome Res., 9, 677–679]. Submissions to dbSNP will be integrated with other sources of information at NCBI such as GenBank, PubMed, LocusLink and the Human Genome Project data. The complete contents of dbSNP are available to the public at website: http://www.ncbi.nlm.nih.gov/SNP. The complete contents of dbSNP can also be downloaded in multiple formats via anonymous FTP at ftp:// ncbi.nlm.nih.gov/snp/.

6,449 citations

Journal ArticleDOI
Yang Zhang1
TL;DR: The I-TASSER server has been developed to generate automated full-length 3D protein structural predictions where the benchmarked scoring system helps users to obtain quantitative assessments of the I- TASSER models.
Abstract: Prediction of 3-dimensional protein structures from amino acid sequences represents one of the most important problems in computational structural biology. The community-wide Critical Assessment of Structure Prediction (CASP) experiments have been designed to obtain an objective assessment of the state-of-the-art of the field, where I-TASSER was ranked as the best method in the server section of the recent 7th CASP experiment. Our laboratory has since then received numerous requests about the public availability of the I-TASSER algorithm and the usage of the I-TASSER predictions. An on-line version of I-TASSER is developed at the KU Center for Bioinformatics which has generated protein structure predictions for thousands of modeling requests from more than 35 countries. A scoring function (C-score) based on the relative clustering structural density and the consensus significance score of multiple threading templates is introduced to estimate the accuracy of the I-TASSER predictions. A large-scale benchmark test demonstrates a strong correlation between the C-score and the TM-score (a structural similarity measurement with values in [0, 1]) of the first models with a correlation coefficient of 0.91. Using a C-score cutoff > -1.5 for the models of correct topology, both false positive and false negative rates are below 0.1. Combining C-score and protein length, the accuracy of the I-TASSER models can be predicted with an average error of 0.08 for TM-score and 2 A for RMSD. The I-TASSER server has been developed to generate automated full-length 3D protein structural predictions where the benchmarked scoring system helps users to obtain quantitative assessments of the I-TASSER models. The output of the I-TASSER server for each query includes up to five full-length models, the confidence score, the estimated TM-score and RMSD, and the standard deviation of the estimations. The I-TASSER server is freely available to the academic community at http://zhang.bioinformatics.ku.edu/I-TASSER .

4,754 citations

Journal ArticleDOI
TL;DR: The quality scores of a protein are displayed in the context of all known protein structures and problematic parts of a structure are shown and highlighted in a 3D molecule viewer in the ProSA-web service.
Abstract: A major problem in structural biology is the recognition of errors in experimental and theoretical models of protein structures. The ProSA program (Protein Structure Analysis) is an established tool which has a large user base and is frequently employed in the refinement and validation of experimental protein structures and in structure prediction and modeling. The analysis of protein structures is generally a difficult and cumbersome exercise. The new service presented here is a straightforward and easy to use extension of the classic ProSA program which exploits the advantages of interactive web-based applications for the display of scores and energy plots that highlight potential problems spotted in protein structures. In particular, the quality scores of a protein are displayed in the context of all known protein structures and problematic parts of a structure are shown and highlighted in a 3D molecule viewer. The service specifically addresses the needs encountered in the validation of protein structures obtained from X-ray analysis, NMR spectroscopy and theoretical calculations. ProSA-web is accessible at https://prosa.services.came.sbg.ac.at.

4,095 citations

Journal ArticleDOI
15 Feb 2003-Proteins
TL;DR: Geometrical validation around the Cα is described, with a new Cβ measure and updated Ramachandran plot, and Favored and allowed ϕ,ψ regions are also defined for Pro, pre‐Pro, and Gly (important because Gly ϕ‐ψ angles are more permissive but less accurately determined).
Abstract: Geometrical validation around the Calpha is described, with a new Cbeta measure and updated Ramachandran plot. Deviation of the observed Cbeta atom from ideal position provides a single measure encapsulating the major structure-validation information contained in bond angle distortions. Cbeta deviation is sensitive to incompatibilities between sidechain and backbone caused by misfit conformations or inappropriate refinement restraints. A new phi,psi plot using density-dependent smoothing for 81,234 non-Gly, non-Pro, and non-prePro residues with B < 30 from 500 high-resolution proteins shows sharp boundaries at critical edges and clear delineation between large empty areas and regions that are allowed but disfavored. One such region is the gamma-turn conformation near +75 degrees,-60 degrees, counted as forbidden by common structure-validation programs; however, it occurs in well-ordered parts of good structures, it is overrepresented near functional sites, and strain is partly compensated by the gamma-turn H-bond. Favored and allowed phi,psi regions are also defined for Pro, pre-Pro, and Gly (important because Gly phi,psi angles are more permissive but less accurately determined). Details of these accurate empirical distributions are poorly predicted by previous theoretical calculations, including a region left of alpha-helix, which rates as favorable in energy yet rarely occurs. A proposed factor explaining this discrepancy is that crowding of the two-peptide NHs permits donating only a single H-bond. New calculations by Hu et al. [Proteins 2002 (this issue)] for Ala and Gly dipeptides, using mixed quantum mechanics and molecular mechanics, fit our nonrepetitive data in excellent detail. To run our geometrical evaluations on a user-uploaded file, see MOLPROBITY (http://kinemage.biochem.duke.edu) or RAMPAGE (http://www-cryst.bioc.cam.ac.uk/rampage).

3,963 citations

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