Abstract
Protein-protein interactions (PPIs) play a major role in many biological processes and they represent an important class of targets for therapeutic intervention. However, targeting PPIs is challenging because often no convenient natural substrates are available as starting point for small-molecule design. Here, we explored the characteristics of protein interfaces in five non-redundant datasets of 174 protein-protein (PP) complexes, and 161 protein-ligand (PL) complexes from the ABC database, 436 PP complexes, and 196 PL complexes from the PIBASE database and a dataset of 89 PL complexes from the Timbal database. In all cases, the small molecule ligands must bind at the respective PP interface. We observed similar amino acid frequencies in all three datasets. Remarkably, also the characteristics of PP contacts and overlapping PL contacts are highly similar.
Highlights
Protein-protein interactions (PPIs) play major roles in many biological processes such as bioenergetics, immune response, signal transduction, structural organization, and apoptosis [1,2]
Unlike established pharmaceutical efforts that are directed, for example, at enzymes, G-protein coupled receptors (GPCR), or ion-channels, PPIs are challenging subjects because there are usually no convenient natural substrates that can be exploited as starting points for small-molecule design
The first pair of datasets consists of 174 PP complexes and 161 PL complexes compiled by Walter et al [15] from the Analysing Biomolecular Contacts (ABC) database [11]. 25 entries of this PL dataset had been updated in the Protein Data Bank (PDB) in the meantime
Summary
Protein-protein interactions (PPIs) play major roles in many biological processes such as bioenergetics, immune response, signal transduction, structural organization, and apoptosis [1,2]. The lack of information about particular interface residues determining the affinities and specificities at such interfaces makes it quite hard to design compounds that are capable of interfering with PPIs. there is a strong need to characterize the properties of protein interfaces that may bind small-molecule ligands and the underlying molecular principles of contacts they are involved in. The Protein Data Bank (PDB) [3] is the primary resource for elucidating the diversity of atomic contacts in protein-protein (PP) and protein-ligand (PL) interactions. Some secondary databases that are derived from the PDB have been created to assist the integrated research on PP and PL interactions. Examples for this are the Timbal database
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