ChemInform Abstract: Discovery of Small Molecule Inhibitors of Protein-Protein Interactions Using Combined Ligand and Target Score Normalization

Autor: Fergal P. Casey, Denis C. Shields, Emilie Pihan
Rok vydání: 2010
Předmět:
Zdroj: ChemInform. 41
ISSN: 1522-2667
0931-7597
DOI: 10.1002/chin.201013209
Popis: Docking experiments of multiple compounds typically focus on a single protein. However, other targets provide information about relative binding efficiencies that is otherwise lacking. We developed a docking strategy that normalized results in both the ligand and target dimensions. This was applied to dock 287 approved small drugs with 35 peptide-binding proteins, including 15 true positives. The combined docking score was normalized by drug and protein and by incorporating information on contact similarity to the template protein−peptide contacts. The 20 top ranking hits included 6 true positives, and three matches with suggestive evidence in the literature: the cardiac glycoside digitoxin may inhibit WW domain interactions, the 14-3-3 ζ protein may bind negatively charged ligands, and the nuclear receptor coactivator site may bind nuclear receptor agonists. Additionally, the Bcl-2 antiapoptotic protein is predicted to bind pargyline, and the antiapoptic p53 interacting protein MDM2 is suggested to bind ...
Databáze: OpenAIRE
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