Linear and Conformational B Cell Epitope Prediction of the HER 2 ECD-Subdomain III by in silico Methods

Abstract

Asian Pacific J Cancer Prev, 13, 3053-3059 IntroductionHuman epidermal growth factor receptor 2 (HER2), also known as ErbB2, c-erbB2 or HER2/neu, is a 185 kDa protein (p185) involved in signal transduction as well as regulating cell growth. Since the discovery of the role of HER2 in tumorigenesis, it has received great attention in cancer research and vaccine design during the past two decades (Tai et al., 2010). HER2 is a transmembrane glycoprotein contains three distinct regions: N-terminal extracellular domain (ECD), a single transmembrane α-helix (TM), and an intracellular tyrosine kinase domain. The largest part of HER2, the N-terminal ECD is composed of approximately 600 residues (90-110 kDa) which could be divided into four subdomains (I-IV). Subdomains I (residues 23-217) and III (343-510) created a binding site for the receptor's potential ligands (Lax, 1988). While the cysteine-rich subdomains II (218-342) and IV (511-582) are involved in the homodimerization and heterodimerization (Fiore, 1987;Pietras, 1995). HER2 is highly expressed in a significant proportion of breast, ovarian, gastric, colon, prostate and lung cancers. HER2 overexpression in these cancers often correlates with

Functional, structural and epitopic prediction of hypothetical proteins of Mycobacterium tuberculosis H37Rv: An in silico approach for prioritizing the targets

“…This is important because the prediction methods use epitope databases to evaluate the methods efficiency. As the prediction results produced by several methods may be different [124], it may be more appropriate to use multiple tools to obtain more consistent and accurate results, which was the approach used in this study. Subsequently, bioinformatics data must be confirmed by laboratory assays so that the information is fed into the databases more accurately.…”

Characterization of Riemerella anatipestifer CH-1 gldJ gene and GldJ protein

“…B-cell epitopes can be categorized into 2 types: linear (continuous) epitopes and conformational (discontinuous) epitopes (Mahdavi et al, 2012). Although the majority of B-cell epitopes are conformational epitopes, the experimental determination of epitopes has primarily focused on the identification of linear B-cell epitopes (El-Manzalawy and Honavar, 2010).…”

Production and Characterization of New Anti-HER2 Monoclonal Antibodies

“…(31,32) Integrated strategy, SUPER-FICIAL software, and PEPOP tool were used for linear and discontinuous B-cell epitope prediction. (31,33,34) In this strategy, a combination of linear B-cell epitope prediction web servers, such as ABCpred, BCPREDs, Bepired, Bcepred, Elliprro, Discotope, and CBtope, were used for prediction of B-cell epitope peptides. (31) In addition, PEPOP, as a newly developed immunoinformatics tool, was used for prediction of discontinuous B-cell epitope peptides.…”

“…Since the MAbs that target different epitopes have distinct biological functions on cancer cells, finding further new epitopes of HER2 ECD is needed. (30) As subdomain III of HER2 ECD plays an important role in the formation of ligand binding site of the receptor and there is no MAb against it, (31) we decided to produce new MAbs from subdomain III of HER2 ECD.…”