NEP: web server for epitope prediction based on antibody neutralization of viral strains with diverse sequences

被引：13

作者：

Chuang, Gwo-Yu ^{[1
]}

Liou, David ^{[2
]}

Kwong, Peter D. ^{[1
]}

Georgiev, Ivelin S. ^{[1
]}

机构：

[1] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA

[2] NIAID, Off Cyber Infrastruct & Computat Biol, NIH, Bethesda, MD 20892 USA

来源：

NUCLEIC ACIDS RESEARCH | 2014年 / 42卷 / W1期

基金：

美国国家卫生研究院;

关键词：

HIV-1; GP120; RATIONAL DESIGN; RESIDUES; BROAD; PERFORMANCE; SITES; PG9;

D O I：

10.1093/nar/gku318

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Delineation of the antigenic site, or epitope, recognized by an antibody can provide clues about functional vulnerabilities and resistance mechanisms, and can therefore guide antibody optimization and epitope-based vaccine design. Previously, we developed an algorithm for antibody-epitope prediction based on antibody neutralization of viral strains with diverse sequences and validated the algorithm on a set of broadly neutralizing HIV-1 antibodies. Here we describe the implementation of this algorithm, NEP (Neutralization-based Epitope Prediction), as a web-based server. The users must supply as input: (i) an alignment of antigen sequences of diverse viral strains; (ii) neutralization data for the antibody of interest against the same set of antigen sequences; and (iii) (optional) a structure of the unbound antigen, for enhanced prediction accuracy. The prediction results can be downloaded or viewed interactively on the antigen structure (if supplied) from the web browser using a JSmol applet. Since neutralization experiments are typically performed as one of the first steps in the characterization of an antibody to determine its breadth and potency, the NEP server can be used to predict antibody-epitope information at no additional experimental costs.

引用

收藏

页码：W64 / W71

页数：8

相关论文

共 30 条

[1] Palivizumab-Resistant Human Respiratory Syncytial Virus Infection in Infancy [J].

Adams, Ortwin ;

Bonzel, Linda ;

Kovacevic, Alexander ;

Mayatepek, Ertan ;

Hoehn, Thomas ;

Vogel, Markus .

CLINICAL INFECTIOUS DISEASES, 2010, 51 (02) :185-188

[2] Partner-Aware Prediction of Interacting Residues in Protein-Protein Complexes from Sequence Data [J].

Ahmad, Shandar ;

Mizuguchi, Kenji .

PLOS ONE, 2011, 6 (12)

[3] Prediction of residues in discontinuous B-cell epitopes using protein 3D structures [J].

Andersen, Pernille Haste ;

Nielsen, Morten ;

Lund, Ole .

PROTEIN SCIENCE, 2006, 15 (11) :2558-2567

[4] The Protein Data Bank [J].

Berman, HM ;

Westbrook, J ;

Feng, Z ;

Gilliland, G ;

Bhat, TN ;

Weissig, H ;

Shindyalov, IN ;

Bourne, PE .

NUCLEIC ACIDS RESEARCH, 2000, 28 (01) :235-242

[5] SPEER-SERVER: a web server for prediction of protein specificity determining sites [J].

Chakraborty, Abhijit ;

Mandloi, Sapan ;

Lanczycki, Christopher J. ;

Panchenko, Anna R. ;

Chakrabarti, Saikat .

NUCLEIC ACIDS RESEARCH, 2012, 40 (W1) :W242-W248

[6] Structure-Based Stabilization of HIV-1 gp120 Enhances Humoral Immune Responses to the Induced Co-Receptor Binding Site [J].

Dey, Barna ;

Svehla, Krisha ;

Xu, Ling ;

Wycuff, Dianne ;

Zhou, Tongqing ;

Voss, Gerald ;

Phogat, Adhuna ;

Chakrabarti, Bimal K. ;

Li, Yuxing ;

Shaw, George ;

Kwong, Peter D. ;

Nabel, Gary J. ;

Mascola, John R. ;

Wyatt, Richard T. .

PLOS PATHOGENS, 2009, 5 (05)

[7] Increasing the Potency and Breadth of an HIV Antibody by Using Structure-Based Rational Design [J].

Diskin, Ron ;

Scheid, Johannes F. ;

Marcovecchio, Paola M. ;

West, Anthony P., Jr. ;

Klein, Florian ;

Gao, Han ;

Gnanapragasam, Priyanthi N. P. ;

Abadir, Alexander ;

Seaman, Michael S. ;

Nussenzweig, Michel C. ;

Bjorkman, Pamela J. .

SCIENCE, 2011, 334 (6060) :1289-1293

[8] Unliganded HIV-1 gp120 core structures assume the CD4-bound conformation with regulation by quaternary interactions and variable loops [J].

Do Kwon, Young ;

Finzi, Andres ;

Wu, Xueling ;

Dogo-Isonagie, Cajetan ;

Lee, Lawrence K. ;

Moore, Lucas R. ;

Schmidt, Stephen D. ;

Stuckey, Jonathan ;

Yang, Yongping ;

Zhou, Tongqing ;

Zhu, Jiang ;

Vicic, David A. ;

Debnath, Asim K. ;

Shapiro, Lawrence ;

Bewley, Carole A. ;

Mascola, John R. ;

Sodroski, Joseph G. ;

Kwong, Peter D. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (15) :5663-5668

[9] Variable Loop Glycan Dependency of the Broad and Potent HIV-1-Neutralizing Antibodies PG9 and PG16 [J].

Doores, Katie J. ;

Burton, Dennis R. .

JOURNAL OF VIROLOGY, 2010, 84 (20) :10510-10521

[10] Computational Prediction of Broadly Neutralizing HIV-1 Antibody Epitopes from Neutralization Activity Data [J].

Ferguson, Andrew L. ;

Falkowska, Emilia ;

Walker, Laura M. ;

Seaman, Michael S. ;

Burton, Dennis R. ;

Chakraborty, Arup K. .

PLOS ONE, 2013, 8 (12)