The iPPI-DB initiative: a community-centered database of protein–protein interaction modulators

Abstract

Motivation One avenue to address the paucity of clinically testable targets is to reinvestigate the druggable genome by tackling complicated types of targets such as Protein-Protein Interactions (PPIs). Given the challenge to target those interfaces with small chemical compounds, it has become clear that learning from successful examples of PPI modulation is a powerful strategy. Freely accessible databases of PPI modulators that provide the community with tractable chemical and pharmacological data, as well as powerful tools to query them, are therefore essential to stimulate new drug discovery projects on PPI targets. Results Here, we present the new version iPPI-DB, our manually curated database of PPI modulators. In this completely redesigned version of the database, we introduce a new web interface relying on crowdsourcing for the maintenance of the database. This interface was created to enable community contributions, whereby external experts can suggest new database entries. Moreover, the data model, the graphical interface, and the tools to query the database have been completely modernized and improved. We added new PPI modulators, new PPI targets and extended our focus to stabilizers of PPIs as well. Availability and implementation The iPPI-DB server is available at https://ippidb.pasteur.fr The source code for this server is available at https://gitlab.pasteur.fr/ippidb/ippidb-web/ and is distributed under GPL licence (http://www.gnu.org/licences/gpl). Queries can be shared through persistent links according to the FAIR data standards. Data can be downloaded from the website as csv files. Supplementary information Supplementary data are available at Bioinformatics online.

Quantitative Estimate Index for Early-Stage Screening of Compounds Targeting Protein-Protein Interactions

“…Therefore, we used iPPI-DB [ 23 ], which was manually curated from the literature. In total, 2361 PPI-targeting compounds are registered in this database (as of 21 April 2021), which are primarily derived from PPI inhibition or stabilization experiments.…”

Challenges in Discovering Drugs That Target the Protein–Protein Interactions of Disordered Proteins

“…However, PPIs are more difficult to therapeutically target than the interactions of globular proteins with other molecules in the cell, because, in general, the interfaces between interacting proteins are (i) highly hydrophobic and larger than the usual receptor-ligand contact areas [7], (ii) flat with few of the grooves that are used in the design of inhibitory molecules, and (iii) have amino acid residues that bind to one another with a high-affinity, which is difficult for small molecules to inhibit [8]. That said, targeting PPIs is increasingly being seen as a promising strategy for the development of new drugs to treat diseases [9,10]. Recently, PPI modulators have entered clinical studies, with some being approved for marketing, indicating that the modulators targeting PPIs have good prospects ( [2] and references therein).…”

InDeep: 3D fully convolutional neural networks to assistin silicodrug design on protein–protein interactions

“…Protein–protein interactions (PPIs) are central elements in numerous biological pathways. They represent increasing interests as therapeutic targets, with a growing number of published studies describing the successful modulation of PPIs using small molecules ( Torchet et al , 2021 ). Yet, identifying chemical probes or drugs on PPIs remains a difficult task.…”