Abstract
Interaction modes and molecular surface properties for both peptide- and protein-antibody complexes have been investigated. Datasets were constituted from the IMGT database and consisted of 37 peptide-antibody (PEPT) and 155 protein-antibody (PROT) complexes. A computer approach was developed to analyze the surface of peptides and proteins using a level set method which allows the characterization of shape complementarity using surface curvature. We found that in both datasets, the interacting surfaces of the two binding partners, exhibited a moderate degree of shape complementarity at the molecular level but not at the atomic level. We also evaluated the structural similarity between peptides bound to antibodies and the corresponding regions in the 3D structures of the cognate proteins. We found that no more than 25% of φ,ψ dihedral angles were conserved between the corresponding regions in peptides and proteins. We also superimposed the parent protein structure onto that of the bound peptides and visually looked for the presence of bumps or clashes between the cognate protein and the antibody. Except for antibodies possessing neutralizing activity and for those bound to a peptide longer than 30 residues, no superimposition in peptide-antibody complexes was found to be bump or clash-free. These findings indicate that studies restricted to continuous epitopes are unlikely to provide the information needed to design short linear peptides that could be expected to mimic satisfactorily the discontinuous epitopes of native proteins and be successful as synthetic vaccines.
Keywords: Synthetic vaccine, level set method, protein-protein interface, protein-ligand recognition, hot spots, structural bioinformatics, x-ray structures
Current Medicinal Chemistry
Title: Structure-Activity Relationships in Peptide-Antibody Complexes: Implications for Epitope Prediction and Development of Synthetic Peptide Vaccines
Volume: 16 Issue: 8
Author(s): Shu-wen W. Chen, Marc H.V. Van Regenmortel and Jean-Luc Pellequer
Affiliation:
Keywords: Synthetic vaccine, level set method, protein-protein interface, protein-ligand recognition, hot spots, structural bioinformatics, x-ray structures
Abstract: Interaction modes and molecular surface properties for both peptide- and protein-antibody complexes have been investigated. Datasets were constituted from the IMGT database and consisted of 37 peptide-antibody (PEPT) and 155 protein-antibody (PROT) complexes. A computer approach was developed to analyze the surface of peptides and proteins using a level set method which allows the characterization of shape complementarity using surface curvature. We found that in both datasets, the interacting surfaces of the two binding partners, exhibited a moderate degree of shape complementarity at the molecular level but not at the atomic level. We also evaluated the structural similarity between peptides bound to antibodies and the corresponding regions in the 3D structures of the cognate proteins. We found that no more than 25% of φ,ψ dihedral angles were conserved between the corresponding regions in peptides and proteins. We also superimposed the parent protein structure onto that of the bound peptides and visually looked for the presence of bumps or clashes between the cognate protein and the antibody. Except for antibodies possessing neutralizing activity and for those bound to a peptide longer than 30 residues, no superimposition in peptide-antibody complexes was found to be bump or clash-free. These findings indicate that studies restricted to continuous epitopes are unlikely to provide the information needed to design short linear peptides that could be expected to mimic satisfactorily the discontinuous epitopes of native proteins and be successful as synthetic vaccines.
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Cite this article as:
Chen W. Shu-wen, Van Regenmortel H.V. Marc and Pellequer Jean-Luc, Structure-Activity Relationships in Peptide-Antibody Complexes: Implications for Epitope Prediction and Development of Synthetic Peptide Vaccines, Current Medicinal Chemistry 2009; 16 (8) . https://dx.doi.org/10.2174/092986709787581914
DOI https://dx.doi.org/10.2174/092986709787581914 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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