charges schemes with CoMFA

[Nicholas Tomkinson <TOMKINSON_NP |-at-| fisonspharm.co.uk>]

           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
           tomkinson_np |-at-| fisonspharm.co.uk