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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

Average CREPIk, CREXPk and PROPk in different k-th surface convex hull layers CHk.CREPIk is the number of epitopes in the k-th convex hull divided by the total number of epitopes in this protein. CREXPk is the number of exposed residues in the 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 k-th convex hull divided by the number of all residues in the k-th convex hull.
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pone.0134835.g006: Average CREPIk, CREXPk and PROPk in different k-th surface convex hull layers CHk.CREPIk is the number of epitopes in the k-th convex hull divided by the total number of epitopes in this protein. CREXPk is the number of exposed residues in the 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 k-th convex hull divided by the number of all residues in the k-th convex hull.

Mentions: Epitopes prefer the outer layer of the protein surface, but not all epitopes are in the first convex hull (CH1(X)) of the protein. Fig 6 shows the average CREPIk, CREXPk and PROPk in the k-th surface convex hull, where k = 1,…15. There are 42.2% of the epitopes in 1st convex hull of the protein (CREPI1 = 42.2%). These 42.2% of epitopes cover 26.0% of the surface area of the protein (CREXP1 = 26.0%). There is approximately one epitope per six residues of CH1 (PROP1 = 17.9%, 1/0.179≈6). We also noted that CREPIk, CREXPk and PROPk are decreased while k is increasing. This indicates that the percentage of epitopes would be decreased when the residue in the protein interior. Take the k = 2 for example; there are 12.6% of the epitopes in the secondary convex hull (CH2). These residues in CH2 cover 7.76% of the protein surface. Each epitope is around 4 non-epitopes.


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)

Average CREPIk, CREXPk and PROPk in different k-th surface convex hull layers CHk.CREPIk is the number of epitopes in the k-th convex hull divided by the total number of epitopes in this protein. CREXPk is the number of exposed residues in the 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 k-th convex hull divided by the number of all residues in the k-th convex hull.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0134835.g006: Average CREPIk, CREXPk and PROPk in different k-th surface convex hull layers CHk.CREPIk is the number of epitopes in the k-th convex hull divided by the total number of epitopes in this protein. CREXPk is the number of exposed residues in the 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 k-th convex hull divided by the number of all residues in the k-th convex hull.
Mentions: Epitopes prefer the outer layer of the protein surface, but not all epitopes are in the first convex hull (CH1(X)) of the protein. Fig 6 shows the average CREPIk, CREXPk and PROPk in the k-th surface convex hull, where k = 1,…15. There are 42.2% of the epitopes in 1st convex hull of the protein (CREPI1 = 42.2%). These 42.2% of epitopes cover 26.0% of the surface area of the protein (CREXP1 = 26.0%). There is approximately one epitope per six residues of CH1 (PROP1 = 17.9%, 1/0.179≈6). We also noted that CREPIk, CREXPk and PROPk are decreased while k is increasing. This indicates that the percentage of epitopes would be decreased when the residue in the protein interior. Take the k = 2 for example; there are 12.6% of the epitopes in the secondary convex hull (CH2). These residues in CH2 cover 7.76% of the protein surface. Each epitope is around 4 non-epitopes.

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