期刊
MEDCHEMCOMM
卷 8, 期 10, 页码 1970-1981出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c7md00381a
关键词
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资金
- AbbVie
- Bayer Pharma AG
- Boehringer Ingelheim
- Canada Foundation for Innovation
- Genome Canada through Ontario Genomics Institute [OGI-055]
- Innovative Medicines Initiative (EU/EFPIA) [ULTRA-DD] [115766]
- Janssen, Merck Co.
- Novartis Pharma AG
- Ontario Ministry of Research, Innovation and Science (MRIS)
- Pfizer
- Sao Paulo Research Foundation-FAPESP
- Takeda
- Wellcome Trust
- Eshelman Institute for Innovation
As the protein databank (PDB) recently passed the cap of 123456 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 11016 unique structures of small-molecule ligands bound to proteins - 6444 of which have experimental binding affinity - representing 750873 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 center dot center dot center dot O hydrogen bonds or the relatively frequent amide-pi stacking between the backbone amide of proteins and aromatic rings of ligands, uncover underused ligand design strategies.
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