Application of EMBM to Structure-Based Design of Warheads for Protease Inhibitors
| Autor: | Tamar Traube, Michael Shokhen, Amnon Albeck |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
chemistry.chemical_classification
Quantitative structure–activity relationship Protease biology Stereochemistry medicine.medical_treatment Organic Chemistry Active site Computer Science Applications Enzyme chemistry Structural Biology Covalent bond Transition state analog Drug Discovery biology.protein medicine Molecular Medicine Structure based |
| Zdroj: | Molecular informatics. 33(1) |
| ISSN: | 1868-1743 |
| Popis: | Most CADD tools handle non-covalent enzyme inhibitors, despite the growing interest of the pharma industry in covalent inhibitors. We have recently introduced an enzyme mechanism-based method, EMBM, as a computational tool for binding trend analysis and prediction of chemical sites (CS) of reversible covalent enzyme inhibitors. In the current study we demonstrate the utility of EMBM to structure-based applications. In this mode, the energy of the enzyme-inhibitor covalent bond is accounted for by the W1 and W2 covalent descriptors we have developed, whereas the non-covalent interactions between the inhibitor CS and the enzyme active site can be estimated directly on the 3D structure of the enzyme-inhibitor complex. |
| Databáze: | OpenAIRE |
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