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Electrostatic models of inhibitory activity
Author(s) -
Grembecka J.,
Kȩdzierski P.,
Sokalski W. A.,
Leszczyński J.
Publication year - 2001
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.1209
Subject(s) - electrostatics , chemistry , quadrupole , dipole , atomic charge , electrostatic interaction , atomic physics , yield (engineering) , ab initio , computational chemistry , chemical physics , physics , thermodynamics , molecule , organic chemistry
Abstract Various models of electrostatic interactions have been applied and tested for several leucine aminopeptidase (LAP) inhibitors interacting with the enzyme active site. Our results indicate that atomic multipoles up to quadrupole moment as well as potential derived Merz–Kollman and RESP charges reproduce reasonably the ab initio electrostatic interaction energies and the expectation values of the molecular electrostatic potential. These electrostatic models together with CHELP atomic point charges, yield the satisfactory correlation of the electrostatic interaction energy with the experimental activities of the inhibitors, in contrast to the results obtained from atomic monopoles (Mulliken charges) and atomic dipoles. Reasonable correlation has been also obtained for the simple electrostatic “key‐lock” model proposed by Náray‐Szabó, in which the LAP active site is represented by set of point charges (“lock”) interacting with the molecular electrostatic potential of each inhibitor (“key”). © 2001 John Wiley & Sons, Inc. Int J Quant Chem 83: 180–192, 2001