Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.747307
Title: Structural and conformational analysis of B-cell epitopes : component to guide peptide vaccine design
Author: Ferdous, Saba
ISNI:       0000 0004 7229 7958
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2018
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Abstract:
Peptide vaccines have many potential advantages including low cost, lack of need for cold-chain storage and safety. However, it is well known that approximately 90% of B-cell Epitopes (BCEs) are discontinuous in nature making it difficult to mimic them for creating vaccines. To perform a detailed structural analysis of these epitopes, they needs to be mapped onto antigen structures that are complexed with antibody. In order to obtain a clean dataset of antibody-antigen complex crystal structures, a pipeline was designed to process automatically and clean the antibody related structures from the PDB. To store this processed antibody structural data, a database (AbDb) was built and made available online. The degree of discontinuity in B-cell epitopes and their conformational nature was studied by mapping epitopes in the antibody-antigen dataset. The discontinuity of B-cell epitopes was analysed by defining extended ‘regions’ (R, consisting of at least 3 antibody-contacting residues each separated by ≤ 3 residues) and small fragments (F, antibody-contacting residues that do not satisfy the requirements for a region). Secondly, an algorithm was developed to classify region shape as linear, curved or folded. Molecular dynamics simulations were carried out on isolated epitope regions (wild type and mutant peptides). The mutant peptides have been designed by mutating non-contacting and hydrophobic residues in epitopes. Two types of mutations (hy- drophobic to alanine and hydrophobic to glutamine) have been studied using molec- ular dynamics simulations. Furthermore, the effect of end-capping on wild type and mutant epitope regions has been studied. Simulation studies were carried out on 5 linear and 5 folded shape regions. Out of these, 2 epitopes (one linear and one folded), along with their mutants and derivatives, were tested experimentally for conformational stability by CD spectroscopy and NMR. The binding of isolated epitopes with antibody was also validated by ELISA and SPR.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.747307  DOI: Not available
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