| Assay Method Information | |
| | Silico Screening Assay |
| Description: | KT1 PH domain small molecule inhibitors were identified using the crystal structure of the AKT1 PH domain bound by PtdIns(1,3,4,5)P4 as descried in Thomas C C, Deak M, Alessi D R, van Aalten D M, High-resolution structure of the pleckstrin homology domain of protein kinase b/AKT bound to phosphatidylinositol (3,4,5)-trisphosphate, Curr Biol 12:1256 (2002), which is hereby incorporated by reference in its entirety, using a pharmacophore query search of the National Cancer Institute database. The high-resolution crystal structure of the isolated PH domain of human AKT1 in complex Ins(1,3,4,5)P4 was utilized to define a pharmacophore pocket for screening using Unity in Sybyl (version 7.2; Tripos Inc., St Louis, Mo.). The pharmacophore pocket included all the residues of the AKT1 crystal structure within 5 Å of the Ins(1,3,4,5)P4 binding site, i.e., Lys14, Arg15, Gly16, Gtu17, Tyr18, Ile19, Lys20, Thr21, Arg23, Pro24, Arg25, Lys39, Pro51, Leu52, Asn53, Asn54, Phe55, Gln79, ile84, Glu85, Arg86 and Phe88, and attributes to various atoms on the ligand and/or protein binding site were assigned. The defined pharmacophore pocket was then used to search virtual chemical databases and candidate compounds were identified. Various docking orientations were analyzed on the basis of FlexX scores, G-score, and X-score. |
| Affinity data for this assay | |
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