Jans Alzate-Morales - Theoretical study on CDK2 inhibitors using a global softness obtained from the density of states

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      Publication Details (including relevant citation   information):

      Source: JOURNAL OF PHYSICAL   CHEMISTRY B Volume: 111 Issue:   12 Pages:   3293-3297 Published:   MAR 29 2007

      Times Cited: 2

      DOI: 10.1021/jp064549h


      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.

      Address (URL): http://pubs.acs.org/doi/abs/10.1021/jp064549h