Subject: charges schemes with CoMFA

From: Nicholas Tomkinson <[email-masked]>
Date: Fri, 03 Feb 1995 15:39:00 +0000 (GMT)

This may be a FAQ but I didn't see anything remotely connected
          to this subject in the archive. If looking at small molecules
          (doing conformational analysis, CoMFA and the like) one needs
          to calculate point charges, what would be the preferred
          method. I want to be consistent throughout the ranges of
          molecules I might look at and time may be an issue so that
          rules out ab initio methods. I have seen papers (Aleman C. et
          al J. Comp. Chem. vol 14 1993 799-808 Besler et al J. Comp.
          Chem. 1990 vol 11 431-439 for example) that suggest that MNDO
          ESP charges show good agreement with ab initio. I can see 2
          disadvantages with this, PM3 seems to be more general than
          MNDO (I often use molecules with sulphur) and ESP seems
          dreadfully slow on my machine. So at the moment I am using PM3
          Mulliken charges. The CoMFA manual suggests that models are
          charge-scheme insensitive but doesnt give any examples. In
          addition, I am using a distance-dependant dielectric but I am
          not convinced this is best for small molecules. Is there
          anyone out there with experience in CoMFA and conformational
          searching in small molecules in particular who either has done
          or has references to validation of any particular charge/non-
          bonded scheme for this sort of study?
          As usual I will summarise if there is anything forthcoming.
          Thanks in advance
          Nick Tomkinson
          [email-masked]