Question about ESP Charges

From: markm.,at,.portal.vpharm.com (Mark Murcko)
Subject: Question about ESP Charges
Date: Thu, 27 Aug 92 22:33:34 EDT

 I have been running G92 calculations lately on fairly large drug
  molecules (15-20 non-hydrogen atoms) and then calculating ESP-
  derived charges using both CHELPG (Thanks, Curt!) and Merz-Singh-
  Kollman (Thanks, Kennie!).
  While I've observed that these methods give similar charges for most
  atoms, there are always a few atoms where the difference is quite
  large -- up to 0.3e.  Also, there is a systematic difference in the
  charges on the hydrogens, with CHELPG giving lower hydrogen charges
  than MZ.  I've been wondering whether anyone can explain why there
  are such differences in the charges, and more importantly, whether
  these differences are likely to cause significant differences in
  the results of the various types of simulations in which people often
  use these charges (for example, conformational analysis of flexible
  molecules in solution).  Has anyone done anything like a systematic
  study of which ESP charge model seems to give the "best results" for
  any kinds of simulations ???
  / Mark
  Mark Murcko
  Vertex Pharmaceuticals Inc.
  Cambridge, MA