Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.22 (cdc2)
 8,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The current work was conducted to investigate the effectiveness of two conceptually distinct in silico ligand-based tools: Partial Least Squares Discriminant Analysis (PLS-DA) and 3D similarity, including shape, physico-chemical and electrostatics to classify target-specific pharmacophores with enrichment power for selective GSK-3 inhibitors against the phylogenetically related CDK-2, CDK-4, CDK-5 and PKC. All virtual screens were performed on four data sets of targets matched pairwise, including selective and nonselective inhibitors for GSK-3. The classification method PLS-DA results revealed that all obtained models are statistically robust according to the cross-validation and response permutation tests. Regarding selective GSK-3 inhibitors differentiation in terms of selectivity (Se), specificity (Sp), and accuracy (ACC), the PLS-DA models for CDK-4/GSK-3, and PKC/GSK-3 datasets are highly efficient discriminative. 3D similarity searches for CDK-4/GSK-3, PKC/GSK-3, and CDK-2/GSK-3 datasets using the most selective reference molecules lead to highest enrichments of selective GSK-3 inhibitors. EON yields excellent early and overall enrichments for ET_ST and ET_combo for most selective query for CDK-4/GSK-3. CDK-5/GSK-3 dataset didn't show consistent statistically significant enrichments for 3D similarity virtual screening. The current methodology is reliable and could be used as a powerful tool for the detection of potentially selective molecules targeting GSK-3.
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PMID:Partial Least Squares Discriminant Analysis and 3D Similarity Perspective Applied to Analyze Comprehensively the Selectivity of Glycogen Synthase Kinase 3 Inhibitors. 3194