PEPOP methods define a set of segments which is usually combined (the path between the segments) starting from one segment (the reference segment)

PEPOP methods define a set of segments which is usually combined (the path between the segments) starting from one segment (the reference segment). factor 1 receptor (IGF-1R) is MGC33570 usually a tyrosine kinase receptor which mediates actions of insulin-like growth factor 1 (IGF-1) [1]. Research and clinical studies have indicated that IGF-1R and its ligands, insulin-like growth factors 1 and 2 (IGF-1 and IGF-2) and insulin have crucial role in the development, maintenance and progression of cancer [2]. Insulin receptor (IR) and IGF-1R share 70% sequence identity. Moreover, IGF-1, IGF-2 and insulin bind to the both receptors [3, 4]. The IGF-1R is usually a transmembrane and heterotetrameric protein consisting of two polypeptide chains; each chain has an extracellular, ligand-binding -subunit and an intracellular -subunit which exhibits tyrosine kinase activity [5]. The extracellular region can SAR125844 be sorted into 6 individual protein domains as follows: N-terminal receptor L domain name (L1), cysteine-rich repeat domain name (CRR), second receptor L domain name (L2), and 3 fibronectin type III domains denoted as FnIII-1, FnIII-2, and FnIII-3 [3, 6, 7]. The IGF-1R over expression in the cancers often correlates with malignancy. This SAR125844 makes the receptor a stylish target for cancer immunotherapy [8]. One of the prevalent strategies to inhibit IGF-1R is the use of MAbs against the extracellular region of the receptor that hinders ligands binding and induces receptor internalization and degradation by endocytosis. However, due to the 70% identity between insulin receptor and the IGF-1R, the MAbs need to be specific inhibitors of the IGF-1R. To date, approximately 31 MAbs for the IGF-1R have been introduced and some of them are in different phases of clinical development [9, 10]. Among them, clinical antibody candidates, such as IMC-A12 (cixutumumab) and BIIB022, inhibited the IGF-1R signalling by blocking the IGF-1 and in some cases the IGF-2 binding and even causing IGF-1R down regulation [11-13]. Although most of these antibodies can inhibit tumor cell proliferation and growth, in vitro and in vivo, with differences in their mechanisms of action, some of them not only did not show any inhibiting effects but also increased ligand binding and stimulated tumor cell growth [10]. Furthermore, there are also some concerns that hyperglycemia can be a potential factor of increased patients morbidity. In phase I testing of cixutumumab, ganitumab and figitumumab on some cancer patients, these MAbs exhibited a toxicity profile with hyperglycemia as the most frequent adverse effect [14-16]. These results urged researchers to conduct more investigations and to develop novel humanized recombinant MAbs for the IGF-1R. The IGF-1R is also considered as a target for vaccine development for primary prevention of murine model of breast cancer. Active immunotherapy with the peptide vaccines which are designed to be chimeric with multi-epitopes of B cells and T helper cells can induce generation of an adaptive immune response [17]. Several experimental techniques are currently available for selection of suitable B cell epitopes. The experimental approaches applied for detecting immunogenic regions are often laborious and resource-intensive. Computational techniques are fast, scalable, and cost-effective for B cell epitopes prediction, for SAR125844 focusing experimental investigations and for better understanding of antigen-antibody interactions [18-20]. Recent researches have shown there are limitations for the current epitope prediction methods. Hence, enhancing ther eliability of computational B cell epitope prediction methods remains a major challenge in computational vaccinology [21]. Nevertheless, prediction results produced by multiple computational tools could be used to gain a consensus result. Basically, the recognition of either small discrete T-cell epitopes or large conformational epitopes recognized by soluble antibodies and B cells, is the key molecular event for the immune response to pathogens [22]. B cell epitopes can be classified into two types: linear (continuous) and conformational (discontinuous). While linear epitopes comprise residues that are continuous in the sequence, conformational epitopes are composed of amino acids that are not neighboring in primary sequence and are brought into close proximity in the folded protein structure [23]. Localization of these epitopes is usually of clinical interest for the development of diagnostic tools, vaccines and cancer immunotherapies [24]. Many attempts have been made for predicting the antigenic sites from certain features of proteins primary structures. Different parameters such as static accessibility,.