Jans Alzate-Morales - A computational study of the protein-ligand interactions in CDK2 inhibitors: Using quantum mechanics/molecular mechanics interaction energy as a predictor of the biological activity

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      Publication Details (including relevant citation   information):

      Source: BIOPHYSICAL JOURNAL Volume: 92 Issue: 2 Pages: 430-439   Published: JAN 2007

      Cited 18 times in SCOPUS

      Abstract:

      We report a combined quantum mechanics/molecular mechanics   (QM/MM) study to determine the protein-ligand interaction energy   between CDK2 (cyclin-dependent kinase 2) and five inhibitors with   the N2-substituted 6-cyclohexylmethoxypurine scaffold.   The computational results in this work show that the QM/MM   interaction energy is strongly correlated to the biological   activity and can be used as a predictor, at least within a family   of substrates. A detailed analysis of the protein-ligand   structures obtained from molecular dynamics simulations shows   specific interactions within the active site that, in some cases,   have not been reported before to our knowledge. The computed   interaction energy gauges the strength of protein-ligand   interactions. Finally, energy decomposition and multiple   regression analyses were performed to check the contribution of   the electrostatic and van der Waals energies to the total   interaction energy and to show the capabilities of the   computational model to identify new potent inhibitors.

      Address (URL): http://www.cell.com/biophysj/retrieve/pii/S0006349507708433