37 research outputs found

    The MEPS server for identifying protein conformational epitopes

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    <p>Abstract</p> <p>Background</p> <p>One of the most interesting problems in molecular immunology is epitope mapping, i.e. the identification of the regions of interaction between an antigen and an antibody. The solution to this problem, even if approximate, would help in designing experiments to precisely map the residues involved in the interaction and could be instrumental both in designing peptides able to mimic the interacting surface of the antigen and in understanding where immunologically important regions are located in its three-dimensional structure. From an experimental point of view, both genetically encoded and chemically synthesised peptide libraries can be used to identify sequences recognized by a given antibody. The problem then arises of which region of a folded protein the selected peptides correspond to.</p> <p>Results</p> <p>We have developed a method able to find the surface region of a protein that can be effectively mimicked by a peptide, given the structure of the protein and the maximum number of side chains deemed to be required for recognition. The method is implemented as a publicly available server. It can also find and report all peptide sequences of a specified length that can mimic the surface of a given protein and store them in a database.</p> <p>The immediate application of the server is the mapping of antibody epitopes, however the system is sufficiently flexible for allowing other questions to be asked, for example one can compare the peptides representing the surface of two proteins known to interact with the same macromolecule to find which is the most likely interacting region.</p> <p>Conclusion</p> <p>We believe that the MEPS server, available at <url>http://www.caspur.it/meps</url>, will be a useful tool for immunologists and structural and computational biologists. We plan to use it ourselves to implement a database of "surface mimicking peptides" for all proteins of known structure and proteins that can be reliably modelled by comparative modelling.</p

    Recent advances in B-cell epitope prediction methods

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    Identification of epitopes that invoke strong responses from B-cells is one of the key steps in designing effective vaccines against pathogens. Because experimental determination of epitopes is expensive in terms of cost, time, and effort involved, there is an urgent need for computational methods for reliable identification of B-cell epitopes. Although several computational tools for predicting B-cell epitopes have become available in recent years, the predictive performance of existing tools remains far from ideal. We review recent advances in computational methods for B-cell epitope prediction, identify some gaps in the current state of the art, and outline some promising directions for improving the reliability of such methods

    Automated Detection of Conformational Epitopes Using Phage Display Peptide Sequences

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    Background: Precise determination of conformational epitopes of neutralizing antibodies represents a key step in the rational design of novel vaccines. A powerful experimental method to gain insights on the physical chemical nature of conformational epitopes is the selection of linear peptides that bind with high affinities to a monoclonal antibody of interest by phage display technology. However, the structural characterization of conformational epitopes from these mimotopes is not straightforward, and in the past the interpretation of peptide sequences from phage display experiments focused on linear sequence analysis to find a consensus sequence or common sequence motifs. Results: We present a fully automated search method, EpiSearch that predicts the possible location of conformational epitopes on the surface of an antigen. The algorithm uses peptide sequences from phage display experiments as input, and ranks all surface exposed patches according to the frequency distribution of similar residues in the peptides and in the patch. We have tested the performance of the EpiSearch algorithm for six experimental data sets of phage display experiments, the human epidermal growth factor receptor-2 (HER-2/neu), the antibody mAb Bo2C11 targeting the C 2 domain of FVIII, antibodies mAb 17b and mAb b12 of the HIV envelope protein gp120, mAb 13b5 targeting HIV-1 capsid protein and 80R of the SARS coronavirus spike protein. In all these examples th

    Bioinformatics Resources and Tools for Conformational B-Cell Epitope Prediction

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    Identification of epitopes which invoke strong humoral responses is an essential issue in the field of immunology. Localizing epitopes by experimental methods is expensive in terms of time, cost, and effort; therefore, computational methods feature for its low cost and high speed was employed to predict B-cell epitopes. In this paper, we review the recent advance of bioinformatics resources and tools in conformational B-cell epitope prediction, including databases, algorithms, web servers, and their applications in solving problems in related areas. To stimulate the development of better tools, some promising directions are also extensively discussed

    PEPOP: Computational design of immunogenic peptides

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    © 2008 Moreau et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

    The role of Mep2 in yeast pseudohyphal growth

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    PhD ThesisIn response to limiting levels of nitrogen in the environment, the diploid yeast Saccharomyces cerevisiae undergoes a dimorphic switch from yeast like growth to filamentous pseudohyphal growth. During this morphological change yeast cells grow as elongated chains of cells attached to each other away from the colony to forage for nutrients. Earlier studies have established the two major signalling pathways that regulate pseudohyphal growth include the MAP Kinase and cAMP-PKA pathways. The Mep2 ammonium transporter is an indispensable but poorly understood element of the pseudohyphal pathway. Although the role of Mep2 in this dimorphic switch has been recognized, the precise molecular mechanisms that link ammonium transport to this dimorphic switch is still unclear. Two distinct models of Mep2 function have been proposed. In the first, pH model, import of substrate during ammonium transport (either ammonium ion, ammonia gas or ammonia gas plus proton) would result in localised cytosolic pH changes which is sensed by an appropriate signal transduction pathway. In the second, transceptor model, Mep2 behaves like a transceptor by undergoing a conformational change during ammonium transport allowing it to physically engage a downstream signalling partner to initiate pseudohyphal growth. The pH model was tested which demonstrates that Mep2 signalling is independent of intracellular pH changes. The genetic screen to identify potential interaction partners of Mep2 identified an interaction between Mep2 and the 14-3-3 protein Bmh1. This interaction has been confirmed using western analysis of membrane fractions and demonstrated that this interaction is lost in signalling deficient Mep2 mutants. The 14-3-3 protein binding site in Mep2 has been identified which is required for the Mep2 dependent activation of the MAP Kinase pathway during pseudohyphal growth. A model for Mep2 sensing is proposed where Mep2 recruits signalling components to the membrane enabling cells to establish polarity where Mep2 is most active.BBSR
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