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Cover Picture: Probing the S1′ Site for the Identification of Non‐Zinc‐Binding MMP‐2 Inhibitors (ChemMedChem 9/2013)
Author(s) -
Pizio Antonella Di,
Laghezza Antonio,
Tortorella Paolo,
Agamen Mariangela
Publication year - 2013
Publication title -
chemmedchem
Language(s) - English
Resource type - Reports
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201390035
Subject(s) - pharmacophore , virtual screening , chemistry , docking (animal) , matrix metalloproteinase , binding site , front cover , hydrogen bond , computational biology , stereochemistry , combinatorial chemistry , molecule , biochemistry , cover (algebra) , biology , medicine , mechanical engineering , nursing , organic chemistry , engineering
The front cover picture shows a virtual screening protocol used to identify non‐zinc‐binding matrix metalloproteinase (MMP)‐2 inhibitors. A virtual library was filtered to obtain a drug‐like subset of molecules that was subsequently submitted to pharmacophore screening, followed by docking in the MMP‐2 (grey protein structure) binding site. The pharmacophore model employed was inspired by a known MMP‐8 inhibitor (green sticks), which was used like a probe in the MMP‐2 S1′ site (top left protein structure). Finally, visual inspection of the docking poses of the virtual hits led to the selection of 20 compounds for experimental evaluation. The virtual screening protocol identified a novel MMP‐2 inhibitor (orange sticks); modeling (bottom left protein structure) suggests that this compound does not bind to the zinc ion (purple sphere), but rather interacts with the target by other means, such as hydrogen bonds (dashed lines). For more details, see the Full Paper by Mariangela Agamennone et al. on p. 1475 ff.