Cited by 42Computational Drug Discovery MethodsChemical Synthesis and AnalysisProtein Structure and Dynamics

Which three-dimensional characteristics make efficient inhibitors of protein–protein interactions?

Kuenemann, Mélaine A., Bourbon, Laura M. L., Labbé, Céline M., Villoutreix, Bruno O., Sperandio, Olivier·2014·Journal of Chemical Information and Modeling

Abstract

The specific properties of protein-protein interactions (PPI) (flat, large and hydrophobic) make them harder to tackle with low-molecular-weight compounds. Learning from the properties of successful examples of PPI interface inhibitors (iPPI) at earlier stages of developments, has been pinpointed as a powerful strategy to circumvent this trend. To this end, we have computationally analyzed the bioactive conformations of iPPI and those of inhibitors of conventional targets (e.g enzymes) to highlight putative iPPI 3D characteristics. Most noticeably, the essential property revealed by this study illustrates how efficiently iPPI manages to bind to the hydrophobic patch often present at the core of protein interfaces. The newly identified properties were further confirmed as characteristics of iPPI using much larger data sets (e.g iPPI-DB, www.ippidb.cdithem.fr ). Interestingly, the absence of correlation of such properties with the hydrophobicity and the size of the compounds opens new ways to design potent iPPI with better pharmacokinetic features.

Integrity signals

Registry

Crossref · 10.1021/ci500487q

Cites

42 of 42 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • HADDOCKPPI is a linear scoring function specifically developed to predict binding affinities of inhibitors of protein-protein interactions (iPPIs).

    “The HADDOCKPPI is a linear scoring function specifically developed to predict binding affinities of inhibitors of protein–protein interactions (iPPIs)”
  • Inhibitors of protein-protein interactions interact in uncommon binding cavities characterized by higher hydrophobicity, aromaticity, and molecular weight compared to enzyme inhibitors, and usually within flatter, larger, and more hydrophobic binding sites than enzyme catalytic sites.

    “which interact in uncommon binding cavities characterized by higher hydrophobicity, aromaticity, and molecular weight compared to enzyme inhibitors, as usually interacting within flatter, larger, and more hydrophobic binding sites than the enzyme catalytic sites (Morelli et al., 2011; Kuenemann et al., 2014).”

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Kuenemann, M. A., Bourbon, L. M. L., Labbé, C. M., Villoutreix, B. O., & Sperandio, O.
Affiliations
  • Inserm (FR)
  • Université Paris Diderot, Sorbonne Paris Cité, UMRS 973 Inserm, Paris 75013, France
Venue
Journal of Chemical Information and Modeling
Published
2014-10-17
Volume
54
Issue
11
Pages
3067-3079
ISSN
  • 1549-9596 (ISSN-L)
  • 1549-960X
OpenAlex
W2018745394
Cited by
42
References
42
Citations by year
2026: 2 · 2022: 4 · 2021: 4 · 2020: 3 · 2019: 3 · 2018: 6 · 2017: 5 · 2016: 7 · 2015: 8
FWCI
6.88
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Chemical Information and Modeling (publishedVersion)
  • PubMed (publishedVersion)
Funders
Agence Nationale de la Recherche (ANR-09-PIRI-0017)
Topics
  • Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords
protein-protein interaction inhibitors, protein-protein interfaces, hydrophobic patch, low molecular weight inhibitors, bioactive conformation, pharmacokinetic properties, inhibitor design
MeSH terms
Models, Molecular, Protein Binding, Protein Conformation, Proteins, Drug Discovery, Hydrophobic and Hydrophilic Interactions

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review