RESUMO
We have previously described a method to predict antigenic epitopes on proteins recognized by specific antibodies. Here we have applied this method to identify epitopes on the NS1 proteins of the four Dengue virus serotypes (DENV1-4) that are bound by a small panel of monoclonal antibodies 1H7.4, 1G5.3 and Gus2. Several epitope regions were predicted for these antibodies and these were found to reflect the experimentally observed reactivities. The known binding epitopes on DENV2 for the antibodies 1H7.4 and 1G5.3 were identified, revealing the reasons for the serotype specificity of 1H7.4 and 1G5.3, and the non-selectivity of Gus2. As DENV NS1 is critical for virus replication and a key vaccine candidate, epitope prediction will be valuable in designing appropriate vaccine control strategies. The ability to predict potential epitopes by computational methods significantly reduces the amount of experimental work required to screen peptide libraries for epitope mapping.
Assuntos
Anticorpos Monoclonais/química , Anticorpos Monoclonais/imunologia , Simulação por Computador , Vírus da Dengue , Mapeamento de Epitopos , Epitopos/química , Epitopos/imunologia , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/imunologia , Sequência de Aminoácidos , Especificidade de Anticorpos/imunologia , Sítios de Ligação , Vírus da Dengue/classificação , Vírus da Dengue/imunologia , Mapeamento de Epitopos/métodos , Modelos Moleculares , Ligação Proteica , Conformação Proteica , Relação Estrutura-AtividadeRESUMO
A series of 2-(alpha-methylbenzylamino) pyrazines have shown to be potent inhibitors of the FMS tyrosine receptor kinase. Details of SAR studies, modeling and synthesis of compounds within this series are reported.
Assuntos
Modelos Moleculares , Pirazinas/síntese química , Pirazinas/farmacologia , Receptor de Fator Estimulador de Colônias de Macrófagos/antagonistas & inibidores , Técnicas de Química Combinatória , Desenho de Fármacos , Estrutura Molecular , Pirazinas/química , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
In this work, we have used a new method to predict the epitopes of HA1 protein of influenza virus to several antibodies HC19, CR9114, BH151 and 4F5. While our results reproduced the binding epitopes of H3N2 or H5N1 for the neutralizing antibodies HC19, CR9114, and BH151 as revealed from the available crystal structures, additional epitopes for these antibodies were also suggested. Moreover, the predicted epitopes of H5N1 HA1 for the newly developed antibody 4F5 are located at the receptor binding domain, while previous study identified a region 76-WLLGNP-81 as the epitope. The possibility of antibody recognition of influenza virus via different mechanism by binding to different epitopes of an antigen is also discussed.
RESUMO
We have recently developed a new method to predict the epitopes of the antigens that are recognized by a specific antibody. In this work, we applied the method to identify the epitopes of the Shiga toxin (Stx2 subunit A) that were bound by two specific antibodies 11E10 and S2C4. The predicted epitopes of Stx2 binding to the antibody 11E10 resembles the recognition surface constructed by the regions of Stx2 identified experimentally. For the S2C4, our results indicate that the antibody recognizes the Stx2 at two different regions on the protein surface. The first region (residues 246-254: ARSVRAVNE) is similar to the recognition region of the 11E10, while the second region is formed by two epitopes. The second region is particularly significant because it includes the amino acid sequence region that is diverse between Stx2 and other Stx (residues 176-188: QREFRQALSETAPV). This new recognition region is believed to play an important role in the experimentally observed selectivity of S2C4 to the Stx2.