title: Theoretical study on CDK2 inhibitors using a global softness obtained from the density of states.
abstract: We report a theoretical study on a series of CDK2 inhibitors using a set of global reactivity indices defined in terms of the density of states. The statistical analysis was performed on the basis of two groups of 11 and 6 compounds, respectively, reported by Hardcastle et al. (J. Med. Chem. 2004, 47, 3710-3722). Both series were classified on the basis of the correlations obtained for the complete set of compounds and the sites targeted within the active site of CDK2. The comparison between the biological activity and the electronic chemical potential approached as the Fermi level yields poor results, thereby suggesting that the interaction between the hinge region (HR) of CDK2 and the ligands may have a marginal contribution from the charge transfer (CT) component. Comparison between the biological activity and global softness shows a better correlation, thereby suggesting that polarization effects outweigh the CT contribution in the HR-ligand interaction. We stress the importance to include in the evaluation of the reactivity indices all of the occupied energy states in order to assess the effects coming from the internal electronic structure involved in the HR-ligand interaction.
authors: Departamento de Química, Facultad de Ciencias, Universidad de Chile, Casilla 653, Santiago, Chile. jalzate@ciq.uchile.cl
authors: Jans H
authors: JH
authors: Alzate-Morales
authors: William
authors: W
authors: Tiznado
authors: Juan C
authors: JC
authors: Santos
authors: Carlos
authors: C
authors: Cárdenas
authors: Renato
authors: R
authors: Contreras
mesh_terms: D000465:Algorithms; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006860:Hydrogen Bonding; D008956:Models, Chemical
chemical_list: D004791:Enzyme Inhibitors; D051357:Cyclin-Dependent Kinase 2