| B cell epitope prediction has been an indispensable means for immunological study. At present, the methods of B cell epitope prediction are mainly based on the primary structure of the antigen protein, and they predict epitopes on basis of the structural characteristics, physicochemical properties of antigen proteins, and so on. But the methods are poor in its accuracy. Molecular docking which studies the protein-protein interactions using surface complementarity is widely used. So the study develops a novel method for B cell epitope prediction based on molecular docking.The main research contents are as follows: Establishment of B cell epitope database, the feasibility analysis of using heterogenous antibody docking for predicting the B cell epitope of influenza virus (A/Aichi/2/68(H3N2)) hemagglutinin, establishment of the method for B cell epitopes prediction, and B cell epitope prediction for GD/1/96 influenza virus hemagglutinin and analysis of antigenic change for HA of GD/1/96 and SX/2/06.First, the PDB was manually searched and filtered. Eventually, a dataset of 62 antibody–antigen co-crystal structures was obtained. and the properties of epitopes for the 62 antibody–antigen co-crystal structures such as the type, amino acid preference, secondary structure, size and area distributions of epitopes were statistical described. This analysis reveals that all of B-cell epitopes in dataset are discontinuous, about 80% of the epitopes constitute 13–21 amino acids spanning an area range of 600–1000A2 , the epitope surface is significantly enriched with charged, and polar amino acids and epitopes are significantly enriched with loops.Second, the protein structures of the non-influenza virus hemagglutinin antibody were docked to the protein structure of the influenza virus hemagglutinin (A/Aichi/2/68(H3N2)) to predict its epitopes, and the RMSD was calculated to analysis the possibility of the method. The results show that the Cαatoms RMSD calculation of interface residues below 0.6 ? after superimposition, and >60% of the antibody-binding site residues are part of a predicted conformational epitope. So molecular docking that predicts B cell discontinuous epitopes could be applied.Third, the method of B cell epitope prediction was established combining the properties of B cell epitopes including hydrophilicity, accessibility, antigenicity, flexibility, secondary structure, amino acid preference and evolutionary conservation with heterogenous antibody docking. And the B cell epitopes of five antigens, each of them have one known epitope, were predicted using the method, the specificity, sensitivity and threshold were computed. The results show that while the specificities of the method are 70%,75%,80%,85%,90%, its sensitivities are 60.5% 48.8%,36.7%,30.9%,20.2%, and the corresponding thresholds are 0.34,0.36,0.39,0.42,0.47 respectively. 0.36 is defined as the threshold and the corresponding specificity and sensitivity is 75% and 48.8%.The last, the B cell epitopes of GD/1/96 HA were predicted using the method. The predicted B cell epitopes of GD/1/96 HA may be consisted with the amino acids as follows: 53R, 66M, 69E, 72N, 84S, 86A, 87N, 115Q, 119K, 120S, 121S, 123S, 126D, 128S, 129S, 131V, 133S, 136P, 137Y, 138H, 139G, 140R, 141S, 152K, 153K, 154N, 155S, 161K, 162R, 167T, 169Q, 185A, 189K, 194P, 218K, 220N, 221G, 236N, 268E, 270E. And those amino acids were clustered for five surfaces on the structure of GD/1/96HA. Combining the results of B cell epitope prediction of GD/1/96 HA with the sequence alignment of GD/1/96 and SX/2/06, the amino acid changes were analyzed on properties of amino acids and steric hindrance. the results show that Q115K, P136S, H138L, S141P, S155N, R162V, A185T, K218Q may be the reason causing the antigenic differences between GD/1/96 and SX/2/06.Established B cell epitopes prediction method, results of GD/1/96 B cell epitopes prediction and analysis of antigenic change for HA of GD/1/96 and SX/2/06 could provide references for the related experiments.
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