Is quantum mechanics necessary for predicting binding free energy?

TitleIs quantum mechanics necessary for predicting binding free energy?
Publication TypeJournal Article
Year of Publication2008
AuthorsZhou T., Huang D., Caflisch A.
JournalJournal of Medicinal Chemistry
Date Published2008 Jul 24
Type of ArticleResearch Article
KeywordsAspartic 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.



Alternate JournalJ. Med. Chem.
PubMed ID18578469
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