Muddassar, M. Pasha, F. A. Neaz, M. M. Saleem, Y. Cho, S. J. 2024-01-20T22:02:18Z 2024-01-20T22:02:18Z 2021-09-03 2009-02 1610-2940 https://pubs.kist.re.kr/handle/201004/132780 Protein kinase B (PKB; also known as Akt kinase) is located downstream in the PI-3 kinase pathway. Overexpression and constitutive activation of PKB/Akt leads to human prostate, breast and ovarian carcinomas. A series of 69 PKB/Akt inhibitors were examined to explore their binding modes using FlexX, and three-dimensional quantitative structure-activity relationship (3D-QSAR) studies based on comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed to provide structural insights into these compounds. CoMFA produced statistically significant results, with cross-validated q (2) and non-cross validated correlation r (2) coefficients of 0.53 and 0.95, respectively. For CoMSIA, steric, hydrophobic and hydrogen bond acceptor fields jointly yielded 'leave one out' q (2) = 0.51 and r (2) = 0.84. The predictive power of CoMFA and CoMSIA was determined using a test set of 13 molecules, which gave correlation coefficients, r(predictive)(2) of 0.58 and 0.62, respectively. Molecular docking revealed that the binding modes of these molecules in the ATP binding sites of the Akt kinase domain were very similar to those of the co-crystallized ligand. The information obtained from 3D contour maps will allow the design of more potent and selective Akt kinase inhibitors. English SPRINGER SIGNAL-TRANSDUCTION ANALYSIS COMSIA AKT QSAR ACTIVATION MECHANISM PHOSPHORYLATION DERIVATIVES VALIDATION PARAMETERS Elucidation of binding mode and three dimensional quantitative structure-activity relationship studies of a novel series of protein kinase B/Akt inhibitors Article 10.1007/s00894-008-0416-7 1 JOURNAL OF MOLECULAR MODELING, v.15, no.2, pp.183 - 192 JOURNAL OF MOLECULAR MODELING 15 2 183 192 scie scopus 000262435000009 2-s2.0-58549120356 Biochemistry & Molecular Biology Biophysics Chemistry, Multidisciplinary Computer Science, Interdisciplinary Applications Biochemistry & Molecular Biology Biophysics Chemistry Computer Science Article SIGNAL-TRANSDUCTION ANALYSIS COMSIA AKT QSAR ACTIVATION MECHANISM PHOSPHORYLATION DERIVATIVES VALIDATION PARAMETERS 3D QSAR Inhibitors Molecular docking Protein kinase B