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Analysis of Conformational B-Cell Epitopes in the Antibody-Antigen Complex Using the Depth Function and the Convex Hull.

Zheng W, Ruan J, Hu G, Wang K, Hanlon M, Gao J - PLoS ONE (2015)

Bottom Line: We found that conformational b-cell epitopes are rich in charged residues Asp, Glu, Lys, Arg, His; aliphatic residues Gly, Pro; non-charged residues Asn, Gln; and aromatic residue Tyr.Conservation of epitopes is not significantly lower than that of exposed non-epitopes.The average depths (obtained by four methods) for epitopes are significantly lower than that of non-epitopes on the surface using the Wilcoxon rank sum test.

View Article: PubMed Central - PubMed

Affiliation: School of Mathematical Sciences and LPMC, Nankai University, Tianjin, People's Republic of China.

ABSTRACT
The prediction of conformational b-cell epitopes plays an important role in immunoinformatics. Several computational methods are proposed on the basis of discrimination determined by the solvent-accessible surface between epitopes and non-epitopes, but the performance of existing methods is far from satisfying. In this paper, depth functions and the k-th surface convex hull are used to analyze epitopes and exposed non-epitopes. On each layer of the protein, we compute relative solvent accessibility and four different types of depth functions, i.e., Chakravarty depth, DPX, half-sphere exposure and half space depth, to analyze the location of epitopes on different layers of the proteins. We found that conformational b-cell epitopes are rich in charged residues Asp, Glu, Lys, Arg, His; aliphatic residues Gly, Pro; non-charged residues Asn, Gln; and aromatic residue Tyr. Conformational b-cell epitopes are rich in coils. Conservation of epitopes is not significantly lower than that of exposed non-epitopes. The average depths (obtained by four methods) for epitopes are significantly lower than that of non-epitopes on the surface using the Wilcoxon rank sum test. Epitopes are more likely to be located in the outer layer of the convex hull of a protein. On the benchmark dataset, the cumulate 10th convex hull covers 84.6% of exposed residues on the protein surface area, and nearly 95% of epitope sites. These findings may be helpful in building a predictor for epitopes.

No MeSH data available.


Related in: MedlinePlus

CREPIk, CREXPk and PROPk curve of CHk with different k values.CREPIk is the number of epitopes on the cumulate k-th convex hull divided by the total number of epitopes in the protein. CREXPk is the number of exposed residues on the cumulate k-th convex hull divided by the number of total exposed residues in the protein. PROPk is defined as the number of epitopes in the cumulate k-th surface convex hull divided by the number of all residues in the cumulate k-th convex hull.
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pone.0134835.g009: CREPIk, CREXPk and PROPk curve of CHk with different k values.CREPIk is the number of epitopes on the cumulate k-th convex hull divided by the total number of epitopes in the protein. CREXPk is the number of exposed residues on the cumulate k-th convex hull divided by the number of total exposed residues in the protein. PROPk is defined as the number of epitopes in the cumulate k-th surface convex hull divided by the number of all residues in the cumulate k-th convex hull.

Mentions: For a given protein, we do not know which K0 of the cumulate k-th convex hull can contain all the epitope sites. If the K0 value is too small, many epitopes will not be considered. On the other hand, if the K0 value is too big, too many non-epitopes will be considered. To estimate a proper K0 value, 7 chains (protein IDs: 1AFV:A, 1FSK:A, 1IAI:M, 1KB5:A, 1NFD:D, 1OTS:A, 1QFU:A) were randomly selected as a test set, and the remaining 50 chains were used as training set. We calculated CREPIk, CREXPk and PROPk of CHk (k = 1, 2,…, 20) for each protein in the training set. Then, averages for three kinds of ratios in CHk were computed. Fig 9 shows the results.


Analysis of Conformational B-Cell Epitopes in the Antibody-Antigen Complex Using the Depth Function and the Convex Hull.

Zheng W, Ruan J, Hu G, Wang K, Hanlon M, Gao J - PLoS ONE (2015)

CREPIk, CREXPk and PROPk curve of CHk with different k values.CREPIk is the number of epitopes on the cumulate k-th convex hull divided by the total number of epitopes in the protein. CREXPk is the number of exposed residues on the cumulate k-th convex hull divided by the number of total exposed residues in the protein. PROPk is defined as the number of epitopes in the cumulate k-th surface convex hull divided by the number of all residues in the cumulate k-th convex hull.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526569&req=5

pone.0134835.g009: CREPIk, CREXPk and PROPk curve of CHk with different k values.CREPIk is the number of epitopes on the cumulate k-th convex hull divided by the total number of epitopes in the protein. CREXPk is the number of exposed residues on the cumulate k-th convex hull divided by the number of total exposed residues in the protein. PROPk is defined as the number of epitopes in the cumulate k-th surface convex hull divided by the number of all residues in the cumulate k-th convex hull.
Mentions: For a given protein, we do not know which K0 of the cumulate k-th convex hull can contain all the epitope sites. If the K0 value is too small, many epitopes will not be considered. On the other hand, if the K0 value is too big, too many non-epitopes will be considered. To estimate a proper K0 value, 7 chains (protein IDs: 1AFV:A, 1FSK:A, 1IAI:M, 1KB5:A, 1NFD:D, 1OTS:A, 1QFU:A) were randomly selected as a test set, and the remaining 50 chains were used as training set. We calculated CREPIk, CREXPk and PROPk of CHk (k = 1, 2,…, 20) for each protein in the training set. Then, averages for three kinds of ratios in CHk were computed. Fig 9 shows the results.

Bottom Line: We found that conformational b-cell epitopes are rich in charged residues Asp, Glu, Lys, Arg, His; aliphatic residues Gly, Pro; non-charged residues Asn, Gln; and aromatic residue Tyr.Conservation of epitopes is not significantly lower than that of exposed non-epitopes.The average depths (obtained by four methods) for epitopes are significantly lower than that of non-epitopes on the surface using the Wilcoxon rank sum test.

View Article: PubMed Central - PubMed

Affiliation: School of Mathematical Sciences and LPMC, Nankai University, Tianjin, People's Republic of China.

ABSTRACT
The prediction of conformational b-cell epitopes plays an important role in immunoinformatics. Several computational methods are proposed on the basis of discrimination determined by the solvent-accessible surface between epitopes and non-epitopes, but the performance of existing methods is far from satisfying. In this paper, depth functions and the k-th surface convex hull are used to analyze epitopes and exposed non-epitopes. On each layer of the protein, we compute relative solvent accessibility and four different types of depth functions, i.e., Chakravarty depth, DPX, half-sphere exposure and half space depth, to analyze the location of epitopes on different layers of the proteins. We found that conformational b-cell epitopes are rich in charged residues Asp, Glu, Lys, Arg, His; aliphatic residues Gly, Pro; non-charged residues Asn, Gln; and aromatic residue Tyr. Conformational b-cell epitopes are rich in coils. Conservation of epitopes is not significantly lower than that of exposed non-epitopes. The average depths (obtained by four methods) for epitopes are significantly lower than that of non-epitopes on the surface using the Wilcoxon rank sum test. Epitopes are more likely to be located in the outer layer of the convex hull of a protein. On the benchmark dataset, the cumulate 10th convex hull covers 84.6% of exposed residues on the protein surface area, and nearly 95% of epitope sites. These findings may be helpful in building a predictor for epitopes.

No MeSH data available.


Related in: MedlinePlus