Surface Accessibility (surface + accessibility)

Distribution by Scientific Domains


Selected Abstracts


An in silico method using an epitope motif database for predicting the location of antigenic determinants on proteins in a structural context

JOURNAL OF MOLECULAR RECOGNITION, Issue 1 2006
Vincent Batori
Abstract Presently X-ray crystallography of protein,antibody complexes is still the most direct way of identifying B-cell epitopes. The objective of this study was to assess the potential of a computer-based epitope mapping tool (EMT) using antigenic amino acid motifs as a fast alternative in a number of applications not requiring detailed information, e.g. development of pharmaceutical proteins, vaccines and industrial enzymes. Using Gal d 4 as a model protein, the EMT was capable of identifying, in the context of the folded protein, amino acid positions known to be involved in antibody binding. The high sensitivity and positive predictive value of the EMT as well as the relevance of the structural associations suggested by the EMT indicated the existence of amino acid motifs that are likely to be involved in antigenic determinants. In addition, differential mapping revealed that sensitivity and positive predictive value were dependent on the minimum relative surface accessibility (RSA) of the amino acids included in the mapping, demonstrating that the EMTs accommodated for the fact that epitopes are three-dimensional entities with various degrees of accessibility. The comparison with existing prediction scales demonstrated the superiority of the EMT with respect to physico-chemical scales. The mapping tool also performed better than the available structural scales, but the significance of the differences remains to be established. Thus, the EMT has the potential of becoming a fast and simple alternative to X-ray crystallography for predicting structural antigenic determinants, if detailed epitope information is not required. Copyright 2005 John Wiley & Sons, Ltd. [source]


Molecular dynamic simulations of nanomechanic chaperone peptide and effects of in silico His mutations on nanostructured function

JOURNAL OF PEPTIDE SCIENCE, Issue 11 2008
Abolfazl Barzegar
Abstract The nanoscale peptide YSGVCHTDLHAWHGDWPLPVK exhibits molecular chaperone activity and prevents protein aggregation under chemical and/or thermal stress. Here, His mutations of this peptide and their impact on chaperone activity were evaluated using theoretical techniques. Molecular dynamic (MD) simulations with simulated annealing (SA) of different mutant nanopeptides were employed to determine the contribution of the scaffolding His residues (H45, H49, H52), when mutated to Pro, on chaperone action in vitro. The in silico mutations of His residues to Pro (H45P, H49P, H52P) revealed loss of secondary ordered strand structure. However, a small part of the strand conformation was formed in the middle region of the native chaperone peptide. The His-to-Pro mutations resulted in decreased gyration radius (Rg) values and surface accessibility of the mutant peptides under the simulation times. The invariant dihedral angle (,) values and the disrupting effects of the Pro residues indicated the coil conformation of mutant peptides. The failure of the chaperone-like action in the Pro mutant peptides was consistent with their decreased effective accessible surfaces. The high variation of , value for His residues in native chaperone peptide leads to high flexibility, such as a minichaperone acting as a nanomachine at the molecular level. Our findings demonstrate that the peptide strand conformation motif with high flexibility at nanoscale is critical for chaperone activity. Copyright 2008 European Peptide Society and John Wiley & Sons, Ltd. [source]


Prediction of residues in discontinuous B-cell epitopes using protein 3D structures

PROTEIN SCIENCE, Issue 11 2006
Pernille Haste Andersen
Abstract Discovery of discontinuous B-cell epitopes is a major challenge in vaccine design. Previous epitope prediction methods have mostly been based on protein sequences and are not very effective. Here, we present DiscoTope, a novel method for discontinuous epitope prediction that uses protein three-dimensional structural data. The method is based on amino acid statistics, spatial information, and surface accessibility in a compiled data set of discontinuous epitopes determined by X-ray crystallography of antibody/antigen protein complexes. DiscoTope is the first method to focus explicitly on discontinuous epitopes. We show that the new structure-based method has a better performance for predicting residues of discontinuous epitopes than methods based solely on sequence information, and that it can successfully predict epitope residues that have been identified by different techniques. DiscoTope detects 15.5% of residues located in discontinuous epitopes with a specificity of 95%. At this level of specificity, the conventional Parker hydrophilicity scale for predicting linear B-cell epitopes identifies only 11.0% of residues located in discontinuous epitopes. Predictions by the DiscoTope method can guide experimental epitope mapping in both rational vaccine design and development of diagnostic tools, and may lead to more efficient epitope identification. [source]


Location of crosslinks in chemically stabilized horseradish peroxidase: Implications for design of crosslinks

BIOTECHNOLOGY & BIOENGINEERING, Issue 4 2001
Anne Marie O'Brien
Abstract The bifunctional compound, ethylene-glycol bis(N -hydroxysuccinimidylsuccinate) (EGNHS), stabilizes horseradish peroxidase C (HRP) by reaction with the enzyme's lysine residues. In this study we compare native and modified HRP by proteolytic fragmentation, peptide sequencing, and mass spectroscopy, and identify the sites of modification. Most significantly, EGNHS is shown to form a crosslink between Lys232 and Lys241 of HRP and modifies Lys174 without formation of a crosslink. These findings are in agreement with the lysine side-chain reactivities predicted from the surface accessibility of the amino groups, and the maximal span of 16 of the EGNHS crosslinker. 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 76: 277,284, 2001. [source]