Tag Archives: GDC-0941

Immunoglobulin molecules specifically recognize particular areas on the surface of proteins.

Immunoglobulin molecules specifically recognize particular areas on the surface of proteins. a semi-automated tool that identified the antigenic interactions within the known antigenCantibody complex structures. We compiled those interactions into Epitome, a database of structure-inferred antigenic residues in proteins. Epitome consists of all known antigen/antibody complex structures, a detailed description of the residues that are involved in the interactions, and their sequence/structure environments. Interactions can be visualized using an interface to Jmol. The database is certainly offered by http://www.rostlab.org/services/epitome/. History ProteinCantigen buildings AntigenCantibody complexes possess long been utilized being a model for understanding the overall sensation of molecular reputation (1C5). The amount of experimental high-resolution 3D buildings of antibodyCantigen complexes in the PDB (6) has significantly increased over the last years. Several groups have used these data to analyze and characterize antigenic interactions, i.e. interactions between the protein (the antigen) and the Complementarity Determining Regions (CDRs) of the antibody (7,8). An important first step in studying antigenic interactions is the characterization of CDRs. MacCallum et al. (8) observed that this hypervariable GDC-0941 loops of CDRs adopt only a limited number of backbone conformations that are determined by a few key residues. Two recent studies have suggested that this amino acid composition and the length of CDRs determine GDC-0941 the type of antigen that can be bound (9,10). Several studies have attempted to differentiate the residues around the antigen surface that are involved in the antigenic conversation from all others (5,7,11). The results of these studies were rather inconsistent. Differences in the data sets chosen (some of which were very small) and in the methodologies may explain some of those inconsistencies. Most importantly, however, the definitions of the CDRs often differed greatly, i.e. if two Ednra studies investigate the same PDB complex and use the same methodology, they might disagree on which of the interactions are antigenic (7). An important ramification of this problem was unveiled GDC-0941 by Blythe and Flower (12), who showed that most existing B-cell epitope prediction methods do not work adequately. One explanation for this observation could be that most methods rely on inaccurate identifications of epitopes. GDC-0941 Definition of the CDRs Antibodies are composed of a skeleton of beta-sheets. Most of the amazing variety of antibodies is usually realized by differences in six hypervariable loops of the CDRs. Therefore, the CDRs have previously been defined through these six loops. The first definition of CDRs was as regions in the Kabat sequence variability plot (13,14). The residues in these regions GDC-0941 are identified through an alignment between the query sequence and a consensus motif for antibodies. Although widely used, the Kabat CDR-definitions can be problematic because CDRs that are in structural loops often have very unusual sequences that are not captured by regular sequence motifs (15). In fact, any method based only on sequence information is usually prone to misaligning and therefore mis-assigning loopy CDRs. Chothia and co-workers (16) therefore based their CDR identification on structural information. Initially, hypervariable loops were defined according to a few structures. Later, the numbering of the residues that was used to locate the CDRs was changed to account for buildings that became obtainable subsequently (17). Research differ within their description of supplementary buildings also, raising the inconsistency in determining hypervariable loops thereby. Extra disadvantages of both Chothia and Kabat et al. method are referred to somewhere else (http://www.bioinf.org.uk/abs/). Right here, we address these nagging problems through a thorough research of most known antigenCantibody complexes in the PDB. Analyzing the buildings, we determined the consensus residues in the antibodies and thus recognized the CDRs on all known proteinCantibody complexes (details below). This initial set of CDRs facilitated the automatic generation of a database with all known antigenic residues in the PDB; we also included the sequence environment and a detailed description of the CDR with which they interact. Several databases of antibodyCantigen complex structures are available (15,18,19). Some of these databases focus on the structural aspects of the conversation (19,20). There are also databases that compile B-cell epitopes without their corresponding antibodies (12,21). However, none of these databases explicitly locates the CDRs or identifies the antigenic residues semi-automatically. In this sense, our resource is usually more comprehensive and very easily flexible to growing data, as more 3D structures of antigenCantibody complexes become available. Thus, the databases mentioned above, particularly the ones that are not structure based, are complementary to Epitome. DATABASE Extraction of 3D structures and identification of.