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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

Minimal level of the convex hull for antigen proteins.Take K0 = 7 for example, there are six proteins for which all epitopes are located in the cumulate 7-th convex hull (CH7).
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pone.0134835.g008: Minimal level of the convex hull for antigen proteins.Take K0 = 7 for example, there are six proteins for which all epitopes are located in the cumulate 7-th convex hull (CH7).

Mentions: K0 is the minimal level of the convex hull such that all epitopes are on the cumulate k-th convex hull (CHk). We analyzed the cumulate k-th convex hull of different antigen protein chains. Fig 8 shows the results. For 24.6% ((1+1+1+3+8)/57, K0≤5) of the antigen chains, all epitopes are covered in the top five layers of the convex hull of the antigen. There are a total of 86.0% ((3+8+7+6+5+7+4+2+3+4)/57 = 86.0%) proteins for which all epitopes are located in top 4~13 layers of the convex hull. This also indicated that there is only one protein for which all epitopes are located in the first layer of the convex hull (CH1). From these results, we can see that the convex hull functions can further describe the distribution of 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)

Minimal level of the convex hull for antigen proteins.Take K0 = 7 for example, there are six proteins for which all epitopes are located in the cumulate 7-th convex hull (CH7).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0134835.g008: Minimal level of the convex hull for antigen proteins.Take K0 = 7 for example, there are six proteins for which all epitopes are located in the cumulate 7-th convex hull (CH7).
Mentions: K0 is the minimal level of the convex hull such that all epitopes are on the cumulate k-th convex hull (CHk). We analyzed the cumulate k-th convex hull of different antigen protein chains. Fig 8 shows the results. For 24.6% ((1+1+1+3+8)/57, K0≤5) of the antigen chains, all epitopes are covered in the top five layers of the convex hull of the antigen. There are a total of 86.0% ((3+8+7+6+5+7+4+2+3+4)/57 = 86.0%) proteins for which all epitopes are located in top 4~13 layers of the convex hull. This also indicated that there is only one protein for which all epitopes are located in the first layer of the convex hull (CH1). From these results, we can see that the convex hull functions can further describe the distribution of 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