Is quantum mechanics necessary for predicting binding free energy?
| Title | Is quantum mechanics necessary for predicting binding free energy? |
| Publication Type | Journal Article |
| Year of Publication | 2008 |
| Authors | Zhou T., Huang D., Caflisch A. |
| Journal | Journal of Medicinal Chemistry |
| Volume | 51 |
| Issue | 14 |
| Pagination | 4280-4288 |
| Date Published | 2008 Jul 24 |
| Type of Article | Research Article |
| Keywords | 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 |
| Abstract | 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. |
| DOI | 10.1021/jm800242q |
| pubindex | 0100 |
| Alternate Journal | J. Med. Chem. |
| PubMed ID | 18578469 |
