From markm@portal.vpharm.com Thu Aug 27 22:46:04 1992
From: markm@portal.vpharm.com (Mark Murcko)
Subject: Question about ESP Charges
To: chemistry@ccl.net
Date: Thu, 27 Aug 92 22:33:34 EDT
Status: R

 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