Virtual docking approaches to protein kinase B inhibition

We examined some in silico approaches to identify Akt (protein kinase B) inhibitors. Experimental validation of selected compounds was achieved using a fluorescence-based enzymatic assay and a substrate phosphorylation assay involving the protein GSK-3. We report on success and failure obtained by using several strategies including FlexX, GOLD, and CSCORE, where the 100-200 top-scoring compounds from a 50000-compound library were experimentally tested. This study led to the identification of low micromolar Akt1 inhibitors.