Quest for the rings. In silico exploration of ring universe to identify novel bioactive heteroaromatic scaffolds
Autor: | Paul Selzer, and Ansgar Schuffenhauer, Stephen Jelfs, Jörg Mühlbacher, Peter Ertl |
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Rok vydání: | 2006 |
Předmět: |
Quantum chemical
Virtual screening Scaffold Molecular model Databases Factual Molecular Structure Chemistry Bioactive molecules In silico Biological Availability Nanotechnology Ring (chemistry) Combinatorial chemistry Hydrocarbons Aromatic Pharmaceutical Preparations Heterocyclic Compounds Drug Design Drug Discovery Molecular Medicine Quantum Theory Neural Networks Computer |
Zdroj: | Journal of medicinal chemistry. 49(15) |
ISSN: | 0022-2623 |
Popis: | Bioactive molecules only contain a relatively limited number of unique ring types. To identify those ring properties and structural characteristics that are necessary for biological activity, a large virtual library of nearly 600 000 heteroaromatic scaffolds was created and characterized by calculated properties, including structural features, bioavailability descriptors, and quantum chemical parameters. A self-organizing neural network was used to cluster these scaffolds and to identify properties that best characterize bioactive ring systems. The analysis shows that bioactivity is very sparsely distributed within the scaffold property and structural space, forming only several relatively small, well-defined "bioactivity islands". Various possible applications of a large database of rings with calculated properties and bioactivity scores in the drug design and discovery process are discussed, including virtual screening, support for the design of combinatorial libraries, bioisosteric design, and scaffold hopping. |
Databáze: | OpenAIRE |
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