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A Systematic Analysis of Atomic Protein-Ligand Interactions in the PDB
- Source :
- Medchemcomm
- Publication Year :
- 2017
- Publisher :
- Cold Spring Harbor Laboratory, 2017.
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Abstract
- We compiled a list of 11 016 unique structures of small-molecule ligands bound to proteins representing 750 873 protein–ligand atomic interactions, and analyzed the frequency, geometry and the impact of each interaction type. The most frequent ligand–protein atom pairs can be clustered into seven interaction types.<br />As the protein databank (PDB) recently passed the cap of 123 456 structures, it stands more than ever as an important resource not only to analyze structural features of specific biological systems, but also to study the prevalence of structural patterns observed in a large body of unrelated structures, that may reflect rules governing protein folding or molecular recognition. Here, we compiled a list of 11 016 unique structures of small-molecule ligands bound to proteins – 6444 of which have experimental binding affinity – representing 750 873 protein–ligand atomic interactions, and analyzed the frequency, geometry and impact of each interaction type. We find that hydrophobic interactions are generally enriched in high-efficiency ligands, but polar interactions are over-represented in fragment inhibitors. While most observations extracted from the PDB will be familiar to seasoned medicinal chemists, less expected findings, such as the high number of C–H···O hydrogen bonds or the relatively frequent amide–π stacking between the backbone amide of proteins and aromatic rings of ligands, uncover underused ligand design strategies.
- Subjects :
- 0301 basic medicine
Stereochemistry
Stacking
Protein Data Bank (RCSB PDB)
Pharmaceutical Science
010402 general chemistry
Biochemistry
01 natural sciences
Hydrophobic effect
03 medical and health sciences
Molecular recognition
Drug Discovery
030304 developmental biology
Pharmacology
0303 health sciences
010405 organic chemistry
Hydrogen bond
Chemistry
Organic Chemistry
Ligand (biochemistry)
Small molecule
0104 chemical sciences
Crystallography
030104 developmental biology
Molecular Medicine
Protein folding
Protein ligand
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Medchemcomm
- Accession number :
- edsair.doi.dedup.....574e27daaf5b1144696cd29f8c28ba16