Prediction of residues in discontinuous B‐cell epitopes using protein 3D structures

Protein Science - Tập 15 Số 11 - Trang 2558-2567 - 2006
P. H. Andersen1, Morten Nielsen1, Ole Lund1
1Center for Biological Sequence Analysis, BioCentrum, Technical University of Denmark, DK-2800 Lyngby, Denmark

Tóm tắt

AbstractDiscovery of discontinuous B‐cell epitopes is a major challenge in vaccine design. Previous epitope prediction methods have mostly been based on protein sequences and are not very effective. Here, we present DiscoTope, a novel method for discontinuous epitope prediction that uses protein three‐dimensional structural data. The method is based on amino acid statistics, spatial information, and surface accessibility in a compiled data set of discontinuous epitopes determined by X‐ray crystallography of antibody/antigen protein complexes. DiscoTope is the first method to focus explicitly on discontinuous epitopes. We show that the new structure‐based method has a better performance for predicting residues of discontinuous epitopes than methods based solely on sequence information, and that it can successfully predict epitope residues that have been identified by different techniques. DiscoTope detects 15.5% of residues located in discontinuous epitopes with a specificity of 95%. At this level of specificity, the conventional Parker hydrophilicity scale for predicting linear B‐cell epitopes identifies only 11.0% of residues located in discontinuous epitopes. Predictions by the DiscoTope method can guide experimental epitope mapping in both rational vaccine design and development of diagnostic tools, and may lead to more efficient epitope identification.

Từ khóa


Tài liệu tham khảo

10.1016/S0264-410X(99)00329-1

10.1093/bioinformatics/18.1.175

10.1093/nar/25.17.3389

10.1073/pnas.0501808102

10.1038/322747a0

10.1002/jmr.752

10.1110/ps.041059505

10.1128/IAI.74.5.2628-2636.2006

10.1007/BF00188344

10.1007/978-1-4899-4541-9

10.1006/jmbi.2001.5036

10.1002/1097-0134(20000901)40:4<572::AID-PROT30>3.0.CO;2-N

10.1073/pnas.78.6.3824

Hubbard S.J., 1993, NACCESS computer program

Jameson B.A., 1988, The antigenic index: A novel algorithm for predicting antigenic determinants, Comput. Appl. Biosci., 4, 181

10.1093/nar/gki460

10.1186/1745-7580-2-2

Leitner T., 2003, HIV sequence compendium 2003, LA‐UR04

10.1093/protein/10.11.1241

Lund O., 2005, Immunological Bioinformatics, 100, 10.7551/mitpress/3679.001.0001

Maksyutov A.Z., 1993, ADEPT: A computer program for prediction of protein antigenic determinants, Comput. Appl. Biosci., 9, 291

10.4049/jimmunol.165.1.331

10.1016/S0969-2126(98)00116-6

10.1093/bioinformatics/bth100

10.1111/j.1399-3011.1980.tb02931.x

10.1073/pnas.83.2.226

10.1002/jmr.602

10.1073/pnas.94.20.10547

10.1073/pnas.86.15.5938

10.1021/bi00367a013

10.1016/0076-6879(91)03010-E

10.1126/science.1107449

10.1074/jbc.M208977200

10.1186/1471-2164-6-79

10.1093/nar/gkj053

10.1002/(SICI)1097-0258(19980430)17:8<857::AID-SIM777>3.0.CO;2-E

10.1002/j.1460-2075.1986.tb04226.x

10.1186/1745-7580-1-4

10.1006/meth.1996.0054

Van Regenmortel M.H., 1994, Predicting antigenic determinants in proteins: Looking for unidimensional solutions to a three‐dimensional problem?, Pept. Res., 7, 224

Thông tin
Thông tin xuất bản

Protein Science

Tập 15 Số 11

2558-2567

Thông tin tác giả