Link to full page (citation export, more details):

Is quantum mechanics necessary for predicting binding free energy?

Full Text PDF:

PDF icon ting08.pdf


PDF icon ting08_s.pdf

T. Zhou; D. Huang; A. Caflisch

Journal: J. Med. Chem.
Year: 2008
Volume: 51
Issue: 14
Pages: 4280-4288
DOI: 10.1021/jm800242q
Type of Publication: Journal Article

Aspartic Acid Endopeptidases; Cyclin-Dependent Kinase 2; Enzyme Inhibitors; HIV-1; Humans; Quantum Theory; RNA Helicases; Serine Endopeptidases; Static Electricity; Viral Nonstructural Proteins; West Nile virus


To take into account polarization effects, the linear interaction energy model with continuum electrostatic solvation (LIECE) is supplemented by the linear-scaling semiempirical quantum mechanical calculation of the intermolecular electrostatic energy (QMLIECE). QMLIECE and LIECE are compared on three enzymes belonging to different classes: the West Nile virus NS3 serine protease (WNV PR), the aspartic protease of the human immunodeficiency virus (HIV-1 PR), and the human cyclin-dependent kinase 2 (CDK2). QMLIECE is superior for 44 peptidic inhibitors of WNV PR because of the different amount of polarization due to the broad range of formal charges of the inhibitors (from 0 to 3). On the other hand, QMLIECE and LIECE show similar accuracy for 24 peptidic inhibitors of HIV-1 PR (20 neutral and 4 with one formal charge) and for 73 CDK2 inhibitors (all neutral). These results indicate that quantum mechanics is essential when the inhibitor/protein complexes have highly variable charge-charge interactions.