Article,
Is quantum mechanics necessary for predicting binding free energy?
J. Med. Chem., (July 2008)
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.
