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Building molecular charge distributions from fragments: Application to HIV‐1 protease inhibitors
Author(s) -
Young L.,
Topol I. A.,
Rashin A. A.,
Burt S. K.
Publication year - 1997
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/(sici)1096-987x(199703)18:4<522::aid-jcc6>3.0.co;2-v
Subject(s) - partial charge , chemistry , molecule , atomic charge , charge (physics) , dipole , computational chemistry , basis set , chemical physics , charge density , computation , density functional theory , physics , quantum mechanics , algorithm , mathematics , organic chemistry
Interaction energies are a function of the molecular charge distribution. In previous work, we found that the set of atomic partial charges giving the best agreement with experimental vacuum dipole moments were from density functional theory calculations using an extended basis set. Extension of such computations to larger molecules requires an atomic partial charge calculation beyond present computational resources. A solution to this problem is the calculation of atomic partial charges for segments of the molecule and reassociation of such fragments to yield partial charges for the entire molecule. Various partitions and reassociation methods for five molecules relevant to HIV‐1 protease inhibitors are examined. A useful method of reassociation is introduced in which atomic partial charges for a large molecule are computed by fitting to the combined electrostatic potential calculated from the fragment partial charges. As expected, the best sites for partitions are shown to be carbon—carbon rather than carbon—nitrogen bonds. © 1997 by John Wiley & Sons, Inc.