title: 3D QSAR studies on GSK-3 inhibition by aloisines.
abstract: GSK-3 is involved in various physiological processes and its inhibitors have been evaluated as promising drug candidates for a lot of unmet pathologies. In this paper, inhibition of GSK-3 by aloisines is investigated by 3D QSAR studies. Two alignment rules were applied to check the influence of spatial alignment of the compounds. Both the CoMFA and CoMSIA techniques were carried out and ASS procedure was applied for CoMFA to find a satisfactory model. The best QSAR model obtained is a CoMSIA model characterized with r(2) of 0.938 and q(2) of 0.673 including steric, electrostatic and hydrophobic fields, possessing good predicting ability. To get a better understanding of the relationship between chemical structure and biological activity, a complex structure of aloisine with GSK-3 was obtained by superimposing GSK-3 into the known cocrystal structure of aloisine-CDK2, and then factors that affect the inhibition activity were investigated further, combining the QSAR study with the complex structure, the results of which are in good accordance and complementary to each other.
authors.affiliation: Key Laboratory for Molecular Design and Nutrition Engineering of Ningbo City, Ningbo Institute of Technology, Zhejiang University, 315100 Ningbo, Zhejiang Province, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Zeng
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Jiang
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.forename: Kewen
authors.initials: K
authors.lastname: Zheng
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.forename: Qingsen
authors.initials: Q
authors.lastname: Yu
mesh_terms: D001665:Binding Sites; D042846:CDC2-CDC28 Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D051357:Cyclin-Dependent Kinase 2; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D011719:Pyrazines / Q000737:chemistry / Q000494:pharmacology*; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D055672:Static Electricity
chemical_list: D004791:Enzyme Inhibitors; D011719:Pyrazines; D011758:Pyrroles; D042846:CDC2-CDC28 Kinases; D051357:Cyclin-Dependent Kinase 2; D038362:Glycogen Synthase Kinase 3