title: Development of in silico models for pyrazoles and pyrimidine derivatives as cyclin-dependent kinase 2 inhibitors.
abstract: CDK₂ (cyclin-dependent kinase 2) is an attractive target for therapeutic intervention in cancer. In this work, quantitative structure-activity relationship (QSAR), molecular docking, and molecular dynamics (MD) studies were performed on three sets of 155 CDK₂ inhibitors. The obtained models exhibit good predictive capability in both internal and external validations (q²=0.73, r²(pred)=0.94 for 6, 6-dimethyl pyrrolo [3,4-c]pyrazoles analogs, q²=0.62, r²(pred)=0.63 for imidazole pyrimidine amides analogs and q²=0.56, r²(pred)=0.58 for 4-(pyrazol-4-yl)-pyrimidines analogs). Furthermore, a comparison between 3D-contour map, docking and MD simulation explore in detail the binding modes and the key structural features impacting the interaction of each series of inhibitors with the CDK₂ enzyme, which should be useful to aid the designing of new inhibitors with CDK₂ improved biological response.
authors.affiliation: Bioinformatics Center, Northwest A&F University, Yangling, Shaanxi 712100,China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Wang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Ma
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Shanna
authors.initials: S
authors.lastname: Zhu
authors.forename: Zhengtao
authors.initials: Z
authors.lastname: Xiao
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000465:Algorithms; D020816:Amino Acid Motifs; D020134:Catalytic Domain; D051357:Cyclin-Dependent Kinase 2 / Q000737:chemistry*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011720:Pyrazoles / Q000737:chemistry*; D011743:Pyrimidines / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D004791:Enzyme Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2