title: Is quantum mechanics necessary for predicting binding free energy?
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.
authors.affiliation: Department of Biochemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhou
authors.forename: Danzhi
authors.initials: D
authors.lastname: Huang
authors.forename: Amedeo
authors.initials: A
authors.lastname: Caflisch
mesh_terms: D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000737:chemistry*; D015497:HIV-1 / Q000201:enzymology; D006801:Humans; D011789:Quantum Theory; D020365:RNA Helicases / Q000037:antagonists & inhibitors; D012697:Serine Endopeptidases; D055672:Static Electricity; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D014902:West Nile virus / Q000201:enzymology; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D016282:Aspartic Acid Endopeptidases; D051357:Cyclin-Dependent Kinase 2; D004791:Enzyme Inhibitors; D020365:RNA Helicases; D012697:Serine Endopeptidases; D017361:Viral Nonstructural Proteins; C060028:NS3 protein, flavivirus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases