Analysis of protein-protein interaction sites using surface patches 1 1Edited by G.Von Heijne

Jones, Susan R.; Thornton, Janet M.

doi:10.1006/jmbi.1997.1234

Cited by 588 publications

(514 citation statements)

References 66 publications

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“…Comparison between epitopes and other types of proteinprotein interfaces in transient hetero-complexes with respect to physico-chemical and structural characteristics (Bogan and Thorn, 1998;Jones and Thornton, 1995, 1996, 1997aNeuvirth et al, 2004), revealed general similarities between the two types of protein regions. Namely, preference for tyrosine and tryptophan residue and unorganized secondary structures was found to characterize both types of interactions.…”

Section: Discussionmentioning

confidence: 99%

“…Epitopes are flatter yet rugged and reside on more convex regions of the antigen surface compared to non-epitope surfaces Based on 6 complexes, (Jones and Thornton, 1997a) Based on 3 antigen structures, (Westhof et al, 1984) remaining antigen surface. In this work, a comprehensive analysis of epitope characteristics was conducted combined with the development of novel computational techniques for this purpose.…”

Section: Discussionmentioning

confidence: 99%

“…A patch was defined as the group of n − 1 residues with the shortest distance to a central residue, where n equals the number of residues in the corresponding epitope (Jones and Thornton, 1997a). The distance between two residues was defined as the minimal Euclidean distance between the centers of any of their exposed atoms.…”

Section: Generation Of Overlapping Patches From the Antigen Surfacementioning

confidence: 99%

“…(For interpretation of the references to color in this figure legend, the reader is referred to the web version of the article.) allel planes encompassing the centers of all exposed patch atoms using the computational geometry algorithms library (CGAL) (http://www.cgal.org); (ii) root mean square deviation (RMSD) of the centers of exposed patch atoms from the least squares plane fitted to the centers of these atoms (Jones and Thornton, 1997a). These measures (illustrated in Fig.…”

Section: At the Patch Levelmentioning

confidence: 99%

“…Although the amount of antibody-antigen co-crystal data remained limited, these analyses revealed general principles of protein-protein interactions, which also had implications for antibody-antigen interactions. Jones and Thornton (1995, 1996, 1997a compared interfaces and non-interface regions with respect to physico-chemical and structural properties at the amino acid level, such as ASA, amino acid composition, degree of protrusion, and flexibility.…”

Section: Introductionmentioning

confidence: 99%

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Computational characterization of B-cell epitopes

Rubinstein

Mayrose

Halperin

et al. 2008

Molecular Immunology

219

233

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Characterizing B-cell epitopes is a fundamental step for understanding the immunological basis of bio-recognition. To date, epitope analyses have either been based on limited structural data, or sequence data alone. In this study, our null hypothesis was that the surface of the antigen is homogeneously antigenic. To test this hypothesis, a large dataset of antibody-antigen complex structures, together with crystal structures of the native antigens, has been compiled. Computational methods were developed and applied to detect and extract physico-chemical, structural, and geometrical properties that may distinguish an epitope from the remaining antigen surface. Rigorous statistical inference was able to clearly reject the null hypothesis showing that epitopes are distinguished from the remaining antigen surface in properties such as amino acid preference, secondary structure composition, geometrical shape, and evolutionary conservation. Specifically, epitopes were found to be significantly enriched with tyrosine and tryptophan, and to show a general preference for charged and polar amino acids. Additionally, epitopes were found to show clear preference for residing on planar parts of the antigen that protrude from the surface, yet with a rugged surface shape at the atom level. The effects of complex formation on the structural properties of the antigen were also computationally characterized and it is shown that epitopes undergo compression upon antibody binding. This correlates with the finding that epitopes are enriched with unorganized secondary structure elements that render them flexible. Thus, this study extends the understanding of the underlying processes required for antibody binding, and reveals new aspects of the antibody-antigen interaction.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Generation Of Overlapping Patches From the Antigen Surfacementioning

confidence: 99%

Section: At the Patch Levelmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Computational characterization of B-cell epitopes

Rubinstein

Mayrose

Halperin

et al. 2008

Molecular Immunology

219

233

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Protein–Protein Interactions as Drug Discovery Targets

Dömling

2010

Burger's Medicinal Chemistry and Drug Discovery

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Protein–protein interactions (PPIs) recently have been recognized as a major class of drug targets. Many of the successful “classical” biotechnology protein drugs are agonists or antagonists of PPIs and there are established pathways for their development. However, small molecular weight compounds as antagonists of PPIs still pose a major problem to discovery due to the inherent physicochemical properties of their targets. Recently, several small molecular weight antagonists of PPIs advanced into clinical trials and thus comprise a proof‐of‐concept to this young area in medicinal chemistry. This chapter summarizes the area of small molecular weight antagonists of PPIs with a focus on recent success stories. After a short introduction into the structural biology of PPIs, recognized important PPI targets, discovery pathways of their inhibitors are discussed. The PPI p53‐Mdm2 with potential applications in cancer is used as a case study to demonstrate to diversity of approaches leading to many different lead structures. In contrast, the discovery of IL‐2/IL‐2 rec. antagonists is discussed to highlight adaptive high affinity binding to hotspot regions.

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Prediction of Protein‐Protein Interactions from Evolutionary Information

Valencia

Pazos

2003

Structural Bioinformatics

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Analysis of protein-protein interaction sites using surface patches 1 1Edited by G.Von Heijne

Cited by 588 publications

References 66 publications

Computational characterization of B-cell epitopes

Computational characterization of B-cell epitopes

Protein–Protein Interactions as Drug Discovery Targets

Prediction of Protein‐Protein Interactions from Evolutionary Information

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